Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the dru...Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.展开更多
Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classificati...Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.展开更多
Objectives The objective of this study was to explore the correlation between the distribution of traditional Chinese medicine(TCM)syndromes and molecular types of breast cancer in the perichemotherapy period.Methods ...Objectives The objective of this study was to explore the correlation between the distribution of traditional Chinese medicine(TCM)syndromes and molecular types of breast cancer in the perichemotherapy period.Methods A total of 325 cases with perichemotherapy breast cancer was classified according to syndrome differentiation in TCM,and R×C table x2 test was used to examine and analyze the relationship between TCM syndromes and molecular types of breast cancer in the perichemotherapy period.Results(1)In the early stage of chemotherapy,there was no significant difference in the distribution of different TCM syndromes among molecular types,mainly liver depression syndrome and liver depression and phlegm coagulation syndrome(p>0.05).(2)In the middle stage of chemotherapy,there were significant differences in the distribution of spleen deficiency and phlegm-dampness syndrome among HER-2 positive(HR positive),HER-2 positive(HR negative),and Luminal Atype,Luminal B type(HER-2 negative),and triple-negative type(p<0.01).(3)After chemotherapy,there were significant differences in the distribution of spleen and kidney yang deficiency syndrome and marrow sea insufficiency syndrome among HER-2 positive(HR negative),triple-negative type,and HER-2 positive(HR positive),Luminal A type,Luminal B type(HER-2 negative),and triple-negative type(p<0.01).Conclusion(1)In the middle stage of chemotherapy,HER-2 positive(HR positive)and HER-2 positive(HR negative)are more likely to show spleen deficiency and phlegmdampness syndrome than other molecular types.(2)In the late stage of chemotherapy,the HER-2 positive(HR negative)and triple-negative type is more likely to show spleenkidney yang deficiency syndrome than other molecular types,and the triple-negative type is more likely to show marrow sea insufficiency syndrome than other molecular types.展开更多
Background:To elucidate the molecular mechanisms of Curcuma longa(C.longa)in breast cancer treatment.Methods:Phytocompounds of C.longa were obtained from Dr.Duke’s Phytochemical and Ethnobotanical Database.Potential ...Background:To elucidate the molecular mechanisms of Curcuma longa(C.longa)in breast cancer treatment.Methods:Phytocompounds of C.longa were obtained from Dr.Duke’s Phytochemical and Ethnobotanical Database.Potential active targets were retrieved from Bindingdb,SEA and Swiss Target Prediction databases.Breast cancer targets were retrieved from the Therapeutic Target Database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were done using DAVID and KOBAS3.0 databases respectively.The Cytoscape software was used to construct the phytocompound-target-pathway network.The PyRx and Desmond software were utilized for molecular docking and molecular dynamics simulation respectively.Results:Out of one hundred and fifty-six phytocompounds,fifty-four modulated proteins involved in breast cancer.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated C.longa exerts its therapeutic effect through regulating several key pathways.Molecular docking analysis revealed that most phytocompounds of C.longa had a good affinity with the key targets.Molecular dynamics simulation showed that ethinylestradiol formed stable ligand-protein complexes.Conclusion:The results of this study will enhance our understanding of the potential molecular mechanisms by which C.longa inhibits breast cancer and lay a foundation for future experimental studies.展开更多
BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targete...BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.展开更多
AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed wit...AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.展开更多
A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast can...A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor (ER), progesterone receptor (PR) and Her-2 status. The prevalence rate of each molecular subtype was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows:luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. How- ever, in the age-specific groups, the age group of ≤35 years was more likely to get basal cell-like cancer (36.9%). Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node (LN) metastasis, tumor stage by American Joint Committee on Cancer (AJCC), radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis (≥1 positive LN) and incidence of high-volume LN metastasis (≥4 positive LN). The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopa-thological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese population.展开更多
BACKGROUND Bitter melon has been used to stop the growth of breast cancer(BRCA)cells.However,the underlying mechanism is still unclear.AIM To predict the therapeutic effect of bitter melon against BRCA using network p...BACKGROUND Bitter melon has been used to stop the growth of breast cancer(BRCA)cells.However,the underlying mechanism is still unclear.AIM To predict the therapeutic effect of bitter melon against BRCA using network pharmacology and to explore the underlying pharmacological mechanisms.METHODS The active ingredients of bitter melon and the related protein targets were taken from the Indian Medicinal Plants,Phytochemistry and Therapeutics and SuperPred databases,respectively.The GeneCards database has been searched for BRCA-related targets.Through an intersection of the drug’s targets and the disease’s objectives,prospective bitter melon anti-BRCA targets were discovered.Gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were carried out to comprehend the biological roles of the target proteins.The binding relationship between bitter melon’s active ingredients and the suggested target proteins was verified using molecular docking techniques.RESULTS Three key substances,momordicoside K,kaempferol,and quercetin,were identified as being important in mediating the putative anti-BRCA effects of bitter melon through the active ingredient-anti-BRCA target network study.Heat shock protein 90 AA,proto-oncogene tyrosine-protein kinase,and signal transducer and activator of transcription 3 were found to be the top three proteins in the proteinprotein interaction network study.The several pathways implicated in the anti-BRCA strategy for an active component include phosphatidylinositol 3-kinase/protein kinase B signaling,transcriptional dysregulation,axon guidance,calcium signaling,focal adhesion,janus kinase-signal transducer and activator of transcription signaling,cyclic adenosine monophosphate signaling,mammalian CONCLUSION Overall,the integration of network pharmacology,molecular docking,and functional enrichment analyses shed light on potential mechanisms underlying bitter melon’s ability to fight BRCA,implicating active ingredients and protein targets,as well as highlighting the major signaling pathways that may be altered by this natural product for therapeutic benefit.展开更多
Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may a...Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.展开更多
Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To est...Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China.Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1,2006 and December 31,2010 from four selected hospitals in Beijing were included and followed up until December 31,2015. Hospitalbased data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index(BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival(OS) and cancer-specific survival(CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival.Results: The 5-year OS and CSS rates for all patients were 89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS rates for patients with stage I, Ⅱ, Ⅲ, and IV diseases were 96.5%, 91.6%, 74.8%, and 40.7%,respectively, and the corresponding estimates of 5-year CSS rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively.The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding estimates of 5-year CSS rates were 93.2%, 89.1 %,85.4%, and 83.5%, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer.Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes.展开更多
Gastric cancer(GC) is a highly heterogenic disease,and it is the second leading cause of cancer death in the world.Common chemotherapies are not very effective for GC,which often presents as an advanced or metastatic ...Gastric cancer(GC) is a highly heterogenic disease,and it is the second leading cause of cancer death in the world.Common chemotherapies are not very effective for GC,which often presents as an advanced or metastatic disease at diagnosis.Treatment options are limited,and the prognosis for advanced GCs is poor.The landscape of genomic alterations in GCs has recently been characterized by several international cancer genome programs,including studies that focused exclusively on GCs in Asians.These studies identified major recurrent driver mutations and provided new insights into the mutational heterogeneity and genetic profiles of GCs.An analysis of gene expression data by the Asian Cancer Research Group(ACRG) further uncovered four distinct molecular subtypes with well-defined clinical features and their intersections with actionable genetic alterations to which targeted therapeutic agents are either already available or under clinical development.In this article,we review the ACRG GC project.We also discuss the implications of the genetic and molecular findings from various GC genomic studies with respect to developing more precise diagnoses and treatment approaches for GCs.展开更多
Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. ...Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.展开更多
Objective: To make a prognostic effect analysis of molecular subtype on young breast cancer patients.Methods: Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecolo...Objective: To make a prognostic effect analysis of molecular subtype on young breast cancer patients.Methods: Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival(DFS) rate, and overall survival(OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses.Results: All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis(43.3%), 126 cases had lymphovascular invasion(67.4%), and 125 cases had histological grade III(66.8%) disease. Twenty-seven cases(14.4%) were Luminal A subtype, 99 cases(52.9%) were Luminal B subtype, 29 cases(15.5%) were human epidermal growth factor receptor 2(HER-2) overexpression subtype, while 32 cases(17.1%) were triple negative breast cancer(TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status(P=0.041) and molecular subtype(P=0.037) were both independent prognostic factors of DFS, while nodal status(P=0.037) and TNBC subtype(P=0.048) were both independent prognostic factors of OS. Conclusions: Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.展开更多
Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast ca...Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.展开更多
Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biolo...Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biological properties. Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24-/low cells, which display stem cell like properties. In the present study, we have isolated breast cancer stem cells from non-metastasis tumor tissue, which is presently at passage 18 and designated as human Breast Cancer Mesenchymal Stem Cells (hBCMSCs) line. These cells showed spindle shaped morphology and formed mammos-pheres as well as pluripotency clones indicating their stem cell nature. Molecular marker study confirmed mesenchymal nature as well as pluripotency, plasticity and oncogenicity of these cells. The hBCMSCs cell line may likely contain a heterogeneous population of malignant cells. Interestingly, we also found that these cells exhibit BRCA 2 mutation, which was found in Indian population. Overall, this study revealed that hBCMSCs cell line may represent a suitable in vitro model to study the mechanism of breast cancer which further leads to an identification of molecular targets for future breast cancer targeted therapy.展开更多
Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplif...Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.展开更多
Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation...Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.展开更多
BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic ...BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.METHODS Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.RESULTS Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets.CONCLUSION DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.展开更多
BACKGROUND Breast cancer(BC)radiogenomics,or correlation analysis of imaging features and BC molecular subtypes,can complement genetic analysis with less resourceintensive diagnostic methods to provide an early and ac...BACKGROUND Breast cancer(BC)radiogenomics,or correlation analysis of imaging features and BC molecular subtypes,can complement genetic analysis with less resourceintensive diagnostic methods to provide an early and accurate triage of BC.This is pertinent because BC is the most prevalent cancer amongst adult women,resulting in rising demands on public health resources.AIM To find combinations of mammogram and ultrasound imaging features that predict BC molecular subtypes in a sample of screening and symptomatic patients.METHODS This retrospective study evaluated 328 consecutive patients in 2017-2018 with histologically confirmed BC,of which 237(72%)presented with symptoms and 91(28%)were detected via a screening program.All the patients underwent mammography and ultrasound imaging prior to biopsy.The images were retrospectively read by two breast-imaging radiologists with 5-10 years of experience with no knowledge of the histology results to ensure statistical independence.To test the hypothesis that imaging features are correlated with tumor subtypes,univariate binomial and multinomial logistic regression models were performed.Our study also used the multivariate logistic regression(with and without interaction terms)to identify combinations of mammogram and ultrasound(US)imaging characteristics predictive of molecular subtypes.RESULTS The presence of circumscribed margins,posterior enhancement,and large size is correlated with triple-negative BC(TNBC),while high-risk microcalcifications and microlobulated margins is predictive of HER2-enriched cancers.Ductal carcinoma in situ is characterized by small size on ultrasound,absence of posterior acoustic features,and architectural distortion on mammogram,while luminal subtypes tend to be small,with spiculated margins and posterior acoustic shadowing(Luminal A type).These results are broadly consistent with findings from prior studies.In addition,we also find that US size signals a higher odds ratio for TNBC if presented during screening.As TNBC tends to display sonographic features such as circumscribed margins and posterior enhancement,resulting in visual similarity with benign common lesions,at the screening stage,size may be a useful factor in deciding whether to recommend a biopsy.CONCLUSION Several imaging features were shown to be independent variables predicting molecular subtypes of BC.Knowledge of such correlations could help clinicians stratify BC patients,possibly enabling earlier treatment or aiding in therapeutic decisions in countries where receptor testing is not readily available.展开更多
Forkhead Box c2(FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer(BLBC, a subtype of breast can...Forkhead Box c2(FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer(BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient's age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index(LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers(71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81502309)。
文摘Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.
文摘Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.
基金supported by 2022 Special Project of Henan ProvinceChineseMedicineScientificResearch(2022ZY1048)2023 Special Project of Henan Province Chinese Medicine Scientific Research(2023YZ2043)Natural Science Foundation of Henan Province(232300421183).
文摘Objectives The objective of this study was to explore the correlation between the distribution of traditional Chinese medicine(TCM)syndromes and molecular types of breast cancer in the perichemotherapy period.Methods A total of 325 cases with perichemotherapy breast cancer was classified according to syndrome differentiation in TCM,and R×C table x2 test was used to examine and analyze the relationship between TCM syndromes and molecular types of breast cancer in the perichemotherapy period.Results(1)In the early stage of chemotherapy,there was no significant difference in the distribution of different TCM syndromes among molecular types,mainly liver depression syndrome and liver depression and phlegm coagulation syndrome(p>0.05).(2)In the middle stage of chemotherapy,there were significant differences in the distribution of spleen deficiency and phlegm-dampness syndrome among HER-2 positive(HR positive),HER-2 positive(HR negative),and Luminal Atype,Luminal B type(HER-2 negative),and triple-negative type(p<0.01).(3)After chemotherapy,there were significant differences in the distribution of spleen and kidney yang deficiency syndrome and marrow sea insufficiency syndrome among HER-2 positive(HR negative),triple-negative type,and HER-2 positive(HR positive),Luminal A type,Luminal B type(HER-2 negative),and triple-negative type(p<0.01).Conclusion(1)In the middle stage of chemotherapy,HER-2 positive(HR positive)and HER-2 positive(HR negative)are more likely to show spleen deficiency and phlegmdampness syndrome than other molecular types.(2)In the late stage of chemotherapy,the HER-2 positive(HR negative)and triple-negative type is more likely to show spleenkidney yang deficiency syndrome than other molecular types,and the triple-negative type is more likely to show marrow sea insufficiency syndrome than other molecular types.
文摘Background:To elucidate the molecular mechanisms of Curcuma longa(C.longa)in breast cancer treatment.Methods:Phytocompounds of C.longa were obtained from Dr.Duke’s Phytochemical and Ethnobotanical Database.Potential active targets were retrieved from Bindingdb,SEA and Swiss Target Prediction databases.Breast cancer targets were retrieved from the Therapeutic Target Database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were done using DAVID and KOBAS3.0 databases respectively.The Cytoscape software was used to construct the phytocompound-target-pathway network.The PyRx and Desmond software were utilized for molecular docking and molecular dynamics simulation respectively.Results:Out of one hundred and fifty-six phytocompounds,fifty-four modulated proteins involved in breast cancer.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated C.longa exerts its therapeutic effect through regulating several key pathways.Molecular docking analysis revealed that most phytocompounds of C.longa had a good affinity with the key targets.Molecular dynamics simulation showed that ethinylestradiol formed stable ligand-protein complexes.Conclusion:The results of this study will enhance our understanding of the potential molecular mechanisms by which C.longa inhibits breast cancer and lay a foundation for future experimental studies.
基金Supported by Agencia Nacional de Investigación y Desarrollo de Chile,Fondo Nacional de Investigación en Salud(FONIS),No.SA20I0059.
文摘BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.
基金Supported by FONACIT Project,No.G2005000408PEII Project,No.2012001201
文摘AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.
文摘A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor (ER), progesterone receptor (PR) and Her-2 status. The prevalence rate of each molecular subtype was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows:luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. How- ever, in the age-specific groups, the age group of ≤35 years was more likely to get basal cell-like cancer (36.9%). Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node (LN) metastasis, tumor stage by American Joint Committee on Cancer (AJCC), radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis (≥1 positive LN) and incidence of high-volume LN metastasis (≥4 positive LN). The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopa-thological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese population.
文摘BACKGROUND Bitter melon has been used to stop the growth of breast cancer(BRCA)cells.However,the underlying mechanism is still unclear.AIM To predict the therapeutic effect of bitter melon against BRCA using network pharmacology and to explore the underlying pharmacological mechanisms.METHODS The active ingredients of bitter melon and the related protein targets were taken from the Indian Medicinal Plants,Phytochemistry and Therapeutics and SuperPred databases,respectively.The GeneCards database has been searched for BRCA-related targets.Through an intersection of the drug’s targets and the disease’s objectives,prospective bitter melon anti-BRCA targets were discovered.Gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were carried out to comprehend the biological roles of the target proteins.The binding relationship between bitter melon’s active ingredients and the suggested target proteins was verified using molecular docking techniques.RESULTS Three key substances,momordicoside K,kaempferol,and quercetin,were identified as being important in mediating the putative anti-BRCA effects of bitter melon through the active ingredient-anti-BRCA target network study.Heat shock protein 90 AA,proto-oncogene tyrosine-protein kinase,and signal transducer and activator of transcription 3 were found to be the top three proteins in the proteinprotein interaction network study.The several pathways implicated in the anti-BRCA strategy for an active component include phosphatidylinositol 3-kinase/protein kinase B signaling,transcriptional dysregulation,axon guidance,calcium signaling,focal adhesion,janus kinase-signal transducer and activator of transcription signaling,cyclic adenosine monophosphate signaling,mammalian CONCLUSION Overall,the integration of network pharmacology,molecular docking,and functional enrichment analyses shed light on potential mechanisms underlying bitter melon’s ability to fight BRCA,implicating active ingredients and protein targets,as well as highlighting the major signaling pathways that may be altered by this natural product for therapeutic benefit.
基金The study design,data collection,data analysis,manuscript preparation,and publication decisions of this work were supported by the Science and Technology Program of Zhejiang Province Traditional Chinese Medicine(2023ZL056,2023ZL409)the Foundation Project of Zhejiang Chinese Medical University(2022JKZKTS26,2022JKJNTZ16,2022JKJNTZ23).
文摘Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.
基金supported by the Beijing Natural Science Foundation (No. 7142139)the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-12M-2-004)+1 种基金the PUMC Youth Fund/Fundamental Research Funds for the Central Universities (No. 3332016033)the National Key Research Program of China (No. 2016YFC1302502)
文摘Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China.Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1,2006 and December 31,2010 from four selected hospitals in Beijing were included and followed up until December 31,2015. Hospitalbased data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index(BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival(OS) and cancer-specific survival(CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival.Results: The 5-year OS and CSS rates for all patients were 89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS rates for patients with stage I, Ⅱ, Ⅲ, and IV diseases were 96.5%, 91.6%, 74.8%, and 40.7%,respectively, and the corresponding estimates of 5-year CSS rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively.The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding estimates of 5-year CSS rates were 93.2%, 89.1 %,85.4%, and 83.5%, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer.Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes.
文摘Gastric cancer(GC) is a highly heterogenic disease,and it is the second leading cause of cancer death in the world.Common chemotherapies are not very effective for GC,which often presents as an advanced or metastatic disease at diagnosis.Treatment options are limited,and the prognosis for advanced GCs is poor.The landscape of genomic alterations in GCs has recently been characterized by several international cancer genome programs,including studies that focused exclusively on GCs in Asians.These studies identified major recurrent driver mutations and provided new insights into the mutational heterogeneity and genetic profiles of GCs.An analysis of gene expression data by the Asian Cancer Research Group(ACRG) further uncovered four distinct molecular subtypes with well-defined clinical features and their intersections with actionable genetic alterations to which targeted therapeutic agents are either already available or under clinical development.In this article,we review the ACRG GC project.We also discuss the implications of the genetic and molecular findings from various GC genomic studies with respect to developing more precise diagnoses and treatment approaches for GCs.
文摘Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.
文摘Objective: To make a prognostic effect analysis of molecular subtype on young breast cancer patients.Methods: Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival(DFS) rate, and overall survival(OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses.Results: All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis(43.3%), 126 cases had lymphovascular invasion(67.4%), and 125 cases had histological grade III(66.8%) disease. Twenty-seven cases(14.4%) were Luminal A subtype, 99 cases(52.9%) were Luminal B subtype, 29 cases(15.5%) were human epidermal growth factor receptor 2(HER-2) overexpression subtype, while 32 cases(17.1%) were triple negative breast cancer(TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status(P=0.041) and molecular subtype(P=0.037) were both independent prognostic factors of DFS, while nodal status(P=0.037) and TNBC subtype(P=0.048) were both independent prognostic factors of OS. Conclusions: Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.
基金supported by National Natural Science Foundation of China(Grant No.81202795)China Postdoctoral Science Foundation(Grant No.2015M571271)
文摘Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.
文摘Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biological properties. Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24-/low cells, which display stem cell like properties. In the present study, we have isolated breast cancer stem cells from non-metastasis tumor tissue, which is presently at passage 18 and designated as human Breast Cancer Mesenchymal Stem Cells (hBCMSCs) line. These cells showed spindle shaped morphology and formed mammos-pheres as well as pluripotency clones indicating their stem cell nature. Molecular marker study confirmed mesenchymal nature as well as pluripotency, plasticity and oncogenicity of these cells. The hBCMSCs cell line may likely contain a heterogeneous population of malignant cells. Interestingly, we also found that these cells exhibit BRCA 2 mutation, which was found in Indian population. Overall, this study revealed that hBCMSCs cell line may represent a suitable in vitro model to study the mechanism of breast cancer which further leads to an identification of molecular targets for future breast cancer targeted therapy.
基金Supported by Grants from the genomics program of the National Research Foundation of Korea funded by the Ministry of ScienceICT+4 种基金and Future PlanningNRF-2012M3A9D1054670 and NRF-2014M3C9A3068554(to Kim SY)Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of EducationNRF-2013R1A1A2006621(to Kim M)the Korea Research Institute of Bioscience and Biotechnology research initiative grant
文摘Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.
基金supported by the National Natural Science Foundation of China (Grant No.81572608 and 81172422)the Wuhan Science and Technology Bureau (Grant No.2017060201010170)
文摘Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
基金Supported by the International Science and Technology Cooperation Projects,No. 2016YFE0107100Capital Special Research Project for Health Development,No. 2014-2-4012+3 种基金Beijing Natural Science Foundation,No. L172055 and No. 7192158National Ten-thousand Talent Programthe Fundamental Research Funds for the Central Universities,No. 3332018032CAMS Innovation Fund for Medical Science (CIFMS),No. 2017-I2M-4-003 and No. 2018-I2M-3-001。
文摘BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.METHODS Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.RESULTS Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets.CONCLUSION DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.
文摘BACKGROUND Breast cancer(BC)radiogenomics,or correlation analysis of imaging features and BC molecular subtypes,can complement genetic analysis with less resourceintensive diagnostic methods to provide an early and accurate triage of BC.This is pertinent because BC is the most prevalent cancer amongst adult women,resulting in rising demands on public health resources.AIM To find combinations of mammogram and ultrasound imaging features that predict BC molecular subtypes in a sample of screening and symptomatic patients.METHODS This retrospective study evaluated 328 consecutive patients in 2017-2018 with histologically confirmed BC,of which 237(72%)presented with symptoms and 91(28%)were detected via a screening program.All the patients underwent mammography and ultrasound imaging prior to biopsy.The images were retrospectively read by two breast-imaging radiologists with 5-10 years of experience with no knowledge of the histology results to ensure statistical independence.To test the hypothesis that imaging features are correlated with tumor subtypes,univariate binomial and multinomial logistic regression models were performed.Our study also used the multivariate logistic regression(with and without interaction terms)to identify combinations of mammogram and ultrasound(US)imaging characteristics predictive of molecular subtypes.RESULTS The presence of circumscribed margins,posterior enhancement,and large size is correlated with triple-negative BC(TNBC),while high-risk microcalcifications and microlobulated margins is predictive of HER2-enriched cancers.Ductal carcinoma in situ is characterized by small size on ultrasound,absence of posterior acoustic features,and architectural distortion on mammogram,while luminal subtypes tend to be small,with spiculated margins and posterior acoustic shadowing(Luminal A type).These results are broadly consistent with findings from prior studies.In addition,we also find that US size signals a higher odds ratio for TNBC if presented during screening.As TNBC tends to display sonographic features such as circumscribed margins and posterior enhancement,resulting in visual similarity with benign common lesions,at the screening stage,size may be a useful factor in deciding whether to recommend a biopsy.CONCLUSION Several imaging features were shown to be independent variables predicting molecular subtypes of BC.Knowledge of such correlations could help clinicians stratify BC patients,possibly enabling earlier treatment or aiding in therapeutic decisions in countries where receptor testing is not readily available.
基金supported by a grant from the National Natural Science Foundation of China(No.30570725)
文摘Forkhead Box c2(FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer(BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient's age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index(LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers(71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.
