Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ES...Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is ...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.展开更多
In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superfic...In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.展开更多
In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving para...In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.展开更多
Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence an...Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence and metastasis often lead to poor prognosis. MicroRNAs are a type of single stranded small molecule RNA with only 18 - 25 nucleotides, which can regulate the expression of various genes and participate in the occurrence and development of tumors. Studies have found that microRNA expression profiling can serve as a reliable and stable biological indicator for early diagnosis and prognosis of tumors. This article provides a review of the research status of MicroRNAs in squamous cell carcinoma of the tongue.展开更多
Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the progn...Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.展开更多
Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinom...Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.展开更多
Squamous cell carcinoma(SCC)of the scalp is the second most prevalent skin cancer,following basal cell carcinoma.Notably,it has the capability to infiltrate the skull,dura mater,and even brain tissue.The cornerstone o...Squamous cell carcinoma(SCC)of the scalp is the second most prevalent skin cancer,following basal cell carcinoma.Notably,it has the capability to infiltrate the skull,dura mater,and even brain tissue.The cornerstone of treatment is the surgical removal of the lesion,with a particular focus on the depth of invasion,which is directly correlated with recurrence rates.Post-surgical strategies may involve immediate or delayed cranial bone reconstruction and repair of scalp defects using either artificial dermis or skin grafts.In the case presented,a substantial defect necessitated more than a single flap for primary repair.Hence,a single pedicle double-island flap was designed for reconstructing the occipital area.Due to increased tension on the flap following cranial bone repair,the bone repair was temporarily deferred.Postoperative care included adjuvant chemotherapy and radiotherapy to mitigate the risk of SCC recurrence.展开更多
Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used...Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0.05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.展开更多
Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell car...Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell carcinoma.Patients with squamous cell carcinoma of the temporal bone are often at advanced stages when diagnosed,and lose the chance for surgery.Neoadjuvant immunotherapy has recently been approved as the first-line treatment for refractory recurrent/metastatic squamous cell carcinoma of the head and neck.However,it remains to be determined whether neoadjuvant immunotherapy can be used as the first-line treatment for temporal bone squamous cell carcinoma to reduce the tumor stage before surgery,or as a palliative treatment for patients with unresectable advanced stage carcinoma.The present study reviews the development of immunotherapy and its clinical application in head and neck squamous cell carcinoma,summarizes the treatment of temporal bone squamous cell carcinoma,and prospects the neoadjuvant immunotherapy as the first-line treatment for temporal bone squamous cell carcinoma.展开更多
Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite th...Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the disease.The presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival patterns.Therapeutic agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient targets.Molecular signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved outcome.In this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.展开更多
BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the b...BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.展开更多
We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of ano...We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.展开更多
Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of...Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.展开更多
Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal g...Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.展开更多
Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT an...Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevan...Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for t...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.展开更多
Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector res...Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector respectively. After the recombinants were transfected into HSC3 and HSC6 with Lipofectamine<sup>TM</sup> MAX, the expression of miR-221/222 and PUMA was analyzed by RT-PCR. The proliferation and migration of HSC3 and HSC6 were detected by CCK-8 assay and Wound-healing assay. Cell cycle and apoptosis were detected by flow cytometry. The effect of the miR-221/222 inhibitor was also assessed in OSCC xenografts in BALB/c-nu mice. Results: Transfection of the miR-221/222 inhibitor increased cell apoptosis and upregulated PUMA expression in OSCC cell lines HSC3 and HSC6 with the significantly reduced expression of miR-221 and miR-222. Furthermore, the miR-221/222 inhibitor suppressed cell growth and invasion and blocked the cell cycle at the G1 phase. Obvious anti-tumor activity was achieved in BALB/c-nu mice by treatment with the miR-221/222 inhibitor, together with the upregulation of PUMA protein in tumors retrieved from the mice. Conclusions: There was a significant inhibitory effect of the miR-221/222 inhibitor on the growth of OSCC both in vitro and in vivo, and there might be a regulatory loop between miR-221/222 and PUMA. These findings demonstrated that downregulation of miR-221/222 could induce cell apoptosis, and it might be considered as a candidate target for gene therapy of OSCC.展开更多
基金Supported by Foundation of Henan Educational Committee,No.22A310024and Natural Science Foundation for Young Teachers'Basic Research of Zhengzhou University,No.JC202035025。
文摘Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009ATianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108+3 种基金National Natural Science Foundation of China,No.82373134Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.
文摘In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.
文摘In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.
文摘Tongue squamous cell carcinoma (TSCC) is the most invasive type of oral malignant tumor, posing a serious threat to human life and health. Its pathogenesis is complex and has a high degree of malignancy. Recurrence and metastasis often lead to poor prognosis. MicroRNAs are a type of single stranded small molecule RNA with only 18 - 25 nucleotides, which can regulate the expression of various genes and participate in the occurrence and development of tumors. Studies have found that microRNA expression profiling can serve as a reliable and stable biological indicator for early diagnosis and prognosis of tumors. This article provides a review of the research status of MicroRNAs in squamous cell carcinoma of the tongue.
基金supported by a grant Hebei Provincial Health Commission project from the Foundation of Basic Research(No.20191843).
文摘Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.
文摘Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.
文摘Squamous cell carcinoma(SCC)of the scalp is the second most prevalent skin cancer,following basal cell carcinoma.Notably,it has the capability to infiltrate the skull,dura mater,and even brain tissue.The cornerstone of treatment is the surgical removal of the lesion,with a particular focus on the depth of invasion,which is directly correlated with recurrence rates.Post-surgical strategies may involve immediate or delayed cranial bone reconstruction and repair of scalp defects using either artificial dermis or skin grafts.In the case presented,a substantial defect necessitated more than a single flap for primary repair.Hence,a single pedicle double-island flap was designed for reconstructing the occipital area.Due to increased tension on the flap following cranial bone repair,the bone repair was temporarily deferred.Postoperative care included adjuvant chemotherapy and radiotherapy to mitigate the risk of SCC recurrence.
文摘Summary: To investigate the expression of hypoxia inducible factor-1 alpha (HIF-1α) and its relationship to apoptosis and proliferation in laryngeal squamous cell carcinoma (LSCC), immunohistochemical method was used to detect the expression of HIF-1α and PCNA. Tunnel technique was used to detect in situ cell apoptosis in LSCC. Our results showed that the expression of HIF-1α was related to the clinical stages of cancer and lymph node metastasis (P<0.05). The relationship between HIF-1α and PCNA was statistically significant (P<0.05) and no relationship was found between HIF-1α and apoptosis (P>0.05) It is concluded that HIF-1α plays a role in the carcinogenesis of laryngeal carcinoma and is correlated with proliferation, but bears no relationship with the apoptosis of tumor cells in LSCC.
基金supported by grants from The National Natural Science Foundation of China(No.81771003 and 82071508).
文摘Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell carcinoma.Patients with squamous cell carcinoma of the temporal bone are often at advanced stages when diagnosed,and lose the chance for surgery.Neoadjuvant immunotherapy has recently been approved as the first-line treatment for refractory recurrent/metastatic squamous cell carcinoma of the head and neck.However,it remains to be determined whether neoadjuvant immunotherapy can be used as the first-line treatment for temporal bone squamous cell carcinoma to reduce the tumor stage before surgery,or as a palliative treatment for patients with unresectable advanced stage carcinoma.The present study reviews the development of immunotherapy and its clinical application in head and neck squamous cell carcinoma,summarizes the treatment of temporal bone squamous cell carcinoma,and prospects the neoadjuvant immunotherapy as the first-line treatment for temporal bone squamous cell carcinoma.
基金supported by ACTREC PhD fellowshipfunded by TMC-IRB (3542)ACTREC annual funds。
文摘Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the disease.The presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival patterns.Therapeutic agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient targets.Molecular signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved outcome.In this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.
基金Supported by MEXT KAKENHI,JP17K09022 and JP20K07643.
文摘BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.
基金supported by the National Nature Science Foundation of China(Grant Numbers 81072214,30371547)the National Key R&D Program of China(Grant Number 2016YFC1102603).
文摘We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.
文摘Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.
基金supported by the Research Funding(No.RCDWJS 2020-20)Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University+1 种基金the Natural Science Foundation of China(81902784&81872207)Sichuan Provincial Fund of China(2022YFSY0058).
文摘Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.
文摘Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.
基金supported by the National Natural Science Foundation of China(Grant No.82173303)Natural Science Foundation of Chongqing,China(Grant No.cstc2021ycjh-bgzxm0149).
文摘Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.
文摘Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector respectively. After the recombinants were transfected into HSC3 and HSC6 with Lipofectamine<sup>TM</sup> MAX, the expression of miR-221/222 and PUMA was analyzed by RT-PCR. The proliferation and migration of HSC3 and HSC6 were detected by CCK-8 assay and Wound-healing assay. Cell cycle and apoptosis were detected by flow cytometry. The effect of the miR-221/222 inhibitor was also assessed in OSCC xenografts in BALB/c-nu mice. Results: Transfection of the miR-221/222 inhibitor increased cell apoptosis and upregulated PUMA expression in OSCC cell lines HSC3 and HSC6 with the significantly reduced expression of miR-221 and miR-222. Furthermore, the miR-221/222 inhibitor suppressed cell growth and invasion and blocked the cell cycle at the G1 phase. Obvious anti-tumor activity was achieved in BALB/c-nu mice by treatment with the miR-221/222 inhibitor, together with the upregulation of PUMA protein in tumors retrieved from the mice. Conclusions: There was a significant inhibitory effect of the miR-221/222 inhibitor on the growth of OSCC both in vitro and in vivo, and there might be a regulatory loop between miR-221/222 and PUMA. These findings demonstrated that downregulation of miR-221/222 could induce cell apoptosis, and it might be considered as a candidate target for gene therapy of OSCC.
