Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of ID...Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.展开更多
BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditi...BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.展开更多
The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages...The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.展开更多
The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ...The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.展开更多
Aim: Ovarian cancer (OC) is a malignant cancer with the highest death rate among various kinds of gynecological tumors. The treatment pattern of HGSCs is mainly primary debulking surgery (PDS), followed by platinum-ba...Aim: Ovarian cancer (OC) is a malignant cancer with the highest death rate among various kinds of gynecological tumors. The treatment pattern of HGSCs is mainly primary debulking surgery (PDS), followed by platinum-based adjuvant chemotherapy, which has been the preferred treatment plan in recent years. Treatment decision-making remains a problem that needs to be addressed. We write this article to summarize the relevant indicators reported and find better decision-making tools. Methods: We have extensively read and understood the literature in the research field involved. We searched for keywords in Pubmed: ovarian cancer;KELIM;chemosensitivity. Later we summarized and organized the current research status in the last two decades. Results: There are many predictors of chemotherapy sensitivity, including pathological chemotherapy response score (CRS), the level of tumor-infiltrating lymphocytes (TILs), BRCA mutations in germ lines or somatic cells, tumor homologous recombination deficiency (HRD), KELIM of CA125 and so on. Many clinical trials have testified that this marker of chemosensitivity all have their own advantages and disadvantages. KELIM of CA125 is low-cost and efficient, which is worth promoting and applying in clinical practice. Conclusions: Many studies have validated the predictive and guiding value of the KELIM of Ca125 in the diagnosis and therapy of ovarian cancer. Nowadays, KELIM of Ca125 is rarely known by clinical doctors and lacks clinical application. We advise that KELIM of CA125 is a potential prognostic factor of ovarian cancer. As a clinical doctor in the process of treating ovarian cancer, we can combine the patient’s situation with KELIM, to develop personalized treatment plans. Not only can it reduce the occurrence of complications, but it can also lower medical costs.展开更多
Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approve...Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.展开更多
Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in...Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.展开更多
The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of ...The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.展开更多
Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent fa...Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.展开更多
Late-stage ovarian cancer(OC)has a poor prognosis and a high metastasis rate,but the underlying molecular mechanism is unclear.RNA binding proteins(RBPs)play important roles in posttranscriptional regulation in the co...Late-stage ovarian cancer(OC)has a poor prognosis and a high metastasis rate,but the underlying molecular mechanism is unclear.RNA binding proteins(RBPs)play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis.In this study,we explored the molecular functions of a canonical RBP,Transformer 2βhomolog(TRA2B),in cancer cells.TRA2B knockdown in HeLa cells and subsequent wholetranscriptome RNA sequencing(RNA-seq)analysis revealed the TRA2B-regulated alternative splicing(AS)profile.We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation,apoptosis and invasion.TRA2B-regulated AS was tightly associated with the mitotic cell cycle,apoptosis and several cancer pathways.Moreover,the expression of hundreds of genes was regulated by TRA2B,and these genes were enriched in the functions of cell proliferation,cell adhesion and angiogenesis,which are related to the malignant phenotype of OC.By integrating the alternatively spliced and differentially expressed genes,we found that AS events and gene expression were regulated independently.We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells.The high TRA2B expression was associated with poor prognosis in patients with OC.In ovarian tissue,TRA2B expression showed a gradual increasing trend with increasing malignancy.We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms,facilitating the targeted treatment of OC.展开更多
Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the ...Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.展开更多
Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them a...Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable.In this study,the differentially expressed genes(DEGs)were identified from an independent GSE69428 Gene Expression Omnibus(GEO)dataset between OC and control samples.The DEGs were processed to construct the protein-protein interaction(PPI)network using STRING.Later,hub genes were identified through Cytohubba analysis of the Cytoscape.Expression and survival profiling of the hub genes were validated using GEPIA,OncoDB,and GENT2.For exploring promoter methylation levels and genetic alterations in hub genes,MEXPRESS and cBioPortal were utilized,respectively.Moreover,DAVID,HPA,TIMER,CancerSEA,ENCORI,DrugBank,and GSCAlite were used for gene enrichment analysis,subcellular localization analysis,immune cell infiltration analysis,exploring correlations between hub genes and different diverse states,lncRNA-miRNA-mRNA co-regulatory network analysis,predicting hub gene-associated drugs,and conducting drug sensitivity analysis,respectively.In total,8947 DEGs were found between OC and normal samples in GSE69428.After STRING and Cytohubba analysis,4 hub genes including TTK(TTK Protein Kinase),(BUB1 mitotic checkpoint serine/threonine kinase B)BUB1B,(Nucleolar and spindle-associated protein 1)NUSAP1,and(ZW10 interacting kinetochore protein)ZWINT were selected as the hub genes.Further,it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls,but overexpression of these genes was not associated with overall survival(OS).However,genetic alterations in those genes were found to be linked with OS and disease-free(DFS)survival.Moreover,this study also revealed some novel links between TTK,BUB1B,NUSAP1,and ZWINT overexpression and promoter methylation status,immune cell infiltration,miRNAs,gene enrichment terms,and various chemotherapeutic drugs.Four hub genes,including TTK,BUB1B,NUSAP1,and ZWINT,were revealed as tumor-promotive factors in OC,having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.展开更多
Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T ...Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis.The single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold screening.Further clustering of T cell-associated clusters revealed four subtypes.Pathways related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T cells.The standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA cohort.The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO.In addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk groups.Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune landscapes.In addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro.Finally,we performed a drug sensitivity analysis and identified six potential drug candidates for OV.To summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.展开更多
Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates ...Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.展开更多
Background:Lotus root polysaccharide is a natural antioxidant.As a new anticancer drug,it has anti-proliferation and pro-apoptotic effects in a variety of tumour cells,but its effect on ovarian cancer is not clear.In ...Background:Lotus root polysaccharide is a natural antioxidant.As a new anticancer drug,it has anti-proliferation and pro-apoptotic effects in a variety of tumour cells,but its effect on ovarian cancer is not clear.In study,we attempted to elucidate the role and mechanism of lotus root polysaccharide in SKOV3 cells.Methods:In this study,the effect of lotus root polysaccharide on mRNA of SKVO3 cells was analyzed by RNA-seq,and verified by Western blot,flow cytometry,fluorescence detection and other techniques.Results:The results showed that lotus root polysaccharide could inhibit the proliferation of ovarian cancer cells.Then,a change in gene expression was found by RNA-seq.In the mRNA(differentially expressed mRNA)with these differences,significant changes in the cell cycle were found by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.Subsequently,the proportion of cells in S phase decreases and G2/M phase increases,as seen with propidium iodide staining.Gene Set Enrichment Analysis showed inhibition of the cell cycle,and the gene and protein expression of CDK1,CCNA1 and CCNB1 were inhibited.Conclusion:Our results show that lotus root polysaccharide can inhibit the growth of SKOV3 cells in vitro by blocking the cell cycle at the G2/M phase,which reveals the potential of lotus root polysaccharide in the treatment of ovarian cancer.展开更多
BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metast...BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.展开更多
Background: The etiology of ovarian cancer is not well-understood;numerous metabolomics profiling, epidemiological, and hospital-based case control studies have associated abnormal levels of blood glucose and serum li...Background: The etiology of ovarian cancer is not well-understood;numerous metabolomics profiling, epidemiological, and hospital-based case control studies have associated abnormal levels of blood glucose and serum lipids with the risk and the prognosis of various types of cancers including ovarian cancer. The association between the risk of the incidence of ovarian cancer and the alterations in the levels of blood glucose and serum lipids is not well defined. Objective: In this study we aimed to compare the levels of blood glucose, triacylglycerols, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with different stages of ovarian cancer and healthy controls to determine how they relate to the risk and prognosis of ovarian cancer. Methodology: In a case-control cross sectional study, we enrolled ninety-nine Sudanese women, diagnosed with ovarian cancer but had not received any kind of treatment as the study group, and a control group of forty-one age-matched, apparently healthy women. The patients were classified according to the International Federation of Obstetricians and Gynecologists staging system into two groups: early stages (stage I & II) and late stages (stages III & IV). Blood glucose and serum lipids;triacylglycerols, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were determined by enzymatic colorimetric methods using commercially available analytical kits. The IBM SPSS version 20 software was used for statistical analysis. A Mann-Whitney U test was used for comparison of the median concentrations of blood glucose, triacylglycerols, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the study groups. Logistic regression model was used to estimate the relative risk of ovarian cancer in relation to levels of blood glucose and serum lipids. P value of 0.05 was considered significant. Results: Our data indicated significantly higher levels of blood glucose (p < 0.001), triacylglycerols (p = 0.002), and low-density lipoprotein cholesterol (p < 0.001), and lower levels of high-density lipoprotein cholesterol (p = 0.023), in ovarian cancer patients compared to the control subjects. No significant difference was found in the levels of blood glucose or any of the serum lipids between patients in the early stages (stage I & II) and those in late stages (stage III & IV) of ovarian cancer. The logistic regression analysis indicated significant association between the elevated levels of the blood glucose, triacylglycerols and low-density lipoprotein cholesterol and the risk of the ovarian cancer. Conclusion: We conclude that the levels of blood glucose, triacylglycerols, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol differ significantly between ovarian cancer patients and the healthy control subjects. The risk of ovarian cancer was positively associated with the levels of blood glucose, triacylglycerols and low-density lipoprotein cholesterol, and negatively associated with levels of high-density lipoprotein cholesterol. Therefore, determination of blood glucose and serum lipids, particularly, triacylglycerols, low-density lipoprotein cholesterol may be helpful as diagnostic indicators of ovarian cancer (OC).展开更多
Ovarian cancer (OC) is the most fatal gynecological malignancy, and identifying reliable prognostic indicators can help guide therapeutic treatment. Various tumor marker-guided treatment regimens can considerably impr...Ovarian cancer (OC) is the most fatal gynecological malignancy, and identifying reliable prognostic indicators can help guide therapeutic treatment. Various tumor marker-guided treatment regimens can considerably improve patient prognosis with a better understanding of the molecular underpinnings of ovarian cancer recurrence and metastasis. Fluorine-18-fluorodeoxyglucose Positron emission tomography/computed tomography (18F-FDG PET/CT) is a molecular imaging tool that provides anatomical and functional information about the tumor, and its volume-based metabolic parameters allow for quantifiable observation of ovarian cancer recurrence, prognosis, and therapeutic efficacy. The combined utilization of serological and radiologic markers has been found to provide increased clinical benefit. This article reviewed the predictive value of serum tumor markers and 18F-FDG PET/CT volumetric metabolic parameters for the prognosis of patients with ovarian cancer.展开更多
Ovarian cancer mostly presents with extensive peritoneal cavity and extraperitoneal dissemination. Satisfactory and complete resection of the lesions is one of the key factors to improve the prognosis. The trend of su...Ovarian cancer mostly presents with extensive peritoneal cavity and extraperitoneal dissemination. Satisfactory and complete resection of the lesions is one of the key factors to improve the prognosis. The trend of surgical resection of extra-ovarian tissues and organs invaded by the tumor has become obvious in order to remove all primary loci and all metastases as much as possible to minimize residual tumor lesions. This article provides a literature review on organ resection in ovarian cancer cytoreduction, summarizing the perioperative complications and survival outcomes at the time of different organ surgery, with the aim of providing guidance for clinical work.展开更多
Ovarian cancer is one of the three major malignant tumors in gynecology, with increasing incidence and mortality rates. Currently, the main treatment methods remain surgical intervention in combination with chemothera...Ovarian cancer is one of the three major malignant tumors in gynecology, with increasing incidence and mortality rates. Currently, the main treatment methods remain surgical intervention in combination with chemotherapy. However, due to its high recurrence rate and the risk of drug resistance, the overall prognosis is poor. Ovarian cancer has been identified as an immunegenic tumor, and in recent years, with the continued advancement of research into immune evasion mechanisms, immunotherapy has emerged as a groundbreaking treatment modality. This article will focus on the immune escape mechanisms and their application in ovarian cancer, providing a comprehensive overview of its current status and the challenges it faces.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81572556 and 81402139).
文摘Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
文摘BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.
文摘The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.
基金supported by Academic Leader Training Program of Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13).
文摘The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.
文摘Aim: Ovarian cancer (OC) is a malignant cancer with the highest death rate among various kinds of gynecological tumors. The treatment pattern of HGSCs is mainly primary debulking surgery (PDS), followed by platinum-based adjuvant chemotherapy, which has been the preferred treatment plan in recent years. Treatment decision-making remains a problem that needs to be addressed. We write this article to summarize the relevant indicators reported and find better decision-making tools. Methods: We have extensively read and understood the literature in the research field involved. We searched for keywords in Pubmed: ovarian cancer;KELIM;chemosensitivity. Later we summarized and organized the current research status in the last two decades. Results: There are many predictors of chemotherapy sensitivity, including pathological chemotherapy response score (CRS), the level of tumor-infiltrating lymphocytes (TILs), BRCA mutations in germ lines or somatic cells, tumor homologous recombination deficiency (HRD), KELIM of CA125 and so on. Many clinical trials have testified that this marker of chemosensitivity all have their own advantages and disadvantages. KELIM of CA125 is low-cost and efficient, which is worth promoting and applying in clinical practice. Conclusions: Many studies have validated the predictive and guiding value of the KELIM of Ca125 in the diagnosis and therapy of ovarian cancer. Nowadays, KELIM of Ca125 is rarely known by clinical doctors and lacks clinical application. We advise that KELIM of CA125 is a potential prognostic factor of ovarian cancer. As a clinical doctor in the process of treating ovarian cancer, we can combine the patient’s situation with KELIM, to develop personalized treatment plans. Not only can it reduce the occurrence of complications, but it can also lower medical costs.
基金funded by Guangzhou Scienceand Information Bureau Item of China(Grant No.201904010013)by Natural Science Foundation of Guangdong Province of China(Grant No.2018A0303130180).
文摘Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.
基金This work was supported by the National Key Research&Development Program of China(No.2021YFC2701402).
文摘Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.
基金supported by the National Natural Science Foundation of China(Grant Nos.NSF-82072876 and NSF-82002618)。
文摘The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of The Third Affiliated Hospital of SouthernMedical University[grant number YM202202].
文摘Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.
基金supported by the National Natural Science Foundation of China(81572563)the National Science Foundations of HUBEI(2018CFB235).
文摘Late-stage ovarian cancer(OC)has a poor prognosis and a high metastasis rate,but the underlying molecular mechanism is unclear.RNA binding proteins(RBPs)play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis.In this study,we explored the molecular functions of a canonical RBP,Transformer 2βhomolog(TRA2B),in cancer cells.TRA2B knockdown in HeLa cells and subsequent wholetranscriptome RNA sequencing(RNA-seq)analysis revealed the TRA2B-regulated alternative splicing(AS)profile.We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation,apoptosis and invasion.TRA2B-regulated AS was tightly associated with the mitotic cell cycle,apoptosis and several cancer pathways.Moreover,the expression of hundreds of genes was regulated by TRA2B,and these genes were enriched in the functions of cell proliferation,cell adhesion and angiogenesis,which are related to the malignant phenotype of OC.By integrating the alternatively spliced and differentially expressed genes,we found that AS events and gene expression were regulated independently.We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells.The high TRA2B expression was associated with poor prognosis in patients with OC.In ovarian tissue,TRA2B expression showed a gradual increasing trend with increasing malignancy.We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms,facilitating the targeted treatment of OC.
基金Suzhou Youth Project of Promoting Health through Science and Education,Grant ID:KJXW2022010.
文摘Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.
基金Researchers Supporting Project Number(RSPD2023R725)King Saud University,Riyadh,Saudi Arabia.
文摘Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable.In this study,the differentially expressed genes(DEGs)were identified from an independent GSE69428 Gene Expression Omnibus(GEO)dataset between OC and control samples.The DEGs were processed to construct the protein-protein interaction(PPI)network using STRING.Later,hub genes were identified through Cytohubba analysis of the Cytoscape.Expression and survival profiling of the hub genes were validated using GEPIA,OncoDB,and GENT2.For exploring promoter methylation levels and genetic alterations in hub genes,MEXPRESS and cBioPortal were utilized,respectively.Moreover,DAVID,HPA,TIMER,CancerSEA,ENCORI,DrugBank,and GSCAlite were used for gene enrichment analysis,subcellular localization analysis,immune cell infiltration analysis,exploring correlations between hub genes and different diverse states,lncRNA-miRNA-mRNA co-regulatory network analysis,predicting hub gene-associated drugs,and conducting drug sensitivity analysis,respectively.In total,8947 DEGs were found between OC and normal samples in GSE69428.After STRING and Cytohubba analysis,4 hub genes including TTK(TTK Protein Kinase),(BUB1 mitotic checkpoint serine/threonine kinase B)BUB1B,(Nucleolar and spindle-associated protein 1)NUSAP1,and(ZW10 interacting kinetochore protein)ZWINT were selected as the hub genes.Further,it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls,but overexpression of these genes was not associated with overall survival(OS).However,genetic alterations in those genes were found to be linked with OS and disease-free(DFS)survival.Moreover,this study also revealed some novel links between TTK,BUB1B,NUSAP1,and ZWINT overexpression and promoter methylation status,immune cell infiltration,miRNAs,gene enrichment terms,and various chemotherapeutic drugs.Four hub genes,including TTK,BUB1B,NUSAP1,and ZWINT,were revealed as tumor-promotive factors in OC,having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.
基金This experiment was supported by the following funds:The Shanghai Municipal Key Clinical Specialty(No.shslczdzk06302)National Natural Science Foundation of China(No.82103029)+1 种基金The Project of The Science and Technology Commission of Shanghai Municipality(No.21ZR1469500)The Shanghai Jiao Tong University Medicine-Engineering Fund(No.YG2021QN137).
文摘Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis.The single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold screening.Further clustering of T cell-associated clusters revealed four subtypes.Pathways related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T cells.The standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA cohort.The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO.In addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk groups.Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune landscapes.In addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro.Finally,we performed a drug sensitivity analysis and identified six potential drug candidates for OV.To summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.
基金supported by the Nature Science Foundation of Ningxia(2020AAC03162).
文摘Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.
基金This work was supported by High Level Talents Research Fund Project of Qingdao Agricultural University in China(No.1120043).
文摘Background:Lotus root polysaccharide is a natural antioxidant.As a new anticancer drug,it has anti-proliferation and pro-apoptotic effects in a variety of tumour cells,but its effect on ovarian cancer is not clear.In study,we attempted to elucidate the role and mechanism of lotus root polysaccharide in SKOV3 cells.Methods:In this study,the effect of lotus root polysaccharide on mRNA of SKVO3 cells was analyzed by RNA-seq,and verified by Western blot,flow cytometry,fluorescence detection and other techniques.Results:The results showed that lotus root polysaccharide could inhibit the proliferation of ovarian cancer cells.Then,a change in gene expression was found by RNA-seq.In the mRNA(differentially expressed mRNA)with these differences,significant changes in the cell cycle were found by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.Subsequently,the proportion of cells in S phase decreases and G2/M phase increases,as seen with propidium iodide staining.Gene Set Enrichment Analysis showed inhibition of the cell cycle,and the gene and protein expression of CDK1,CCNA1 and CCNB1 were inhibited.Conclusion:Our results show that lotus root polysaccharide can inhibit the growth of SKOV3 cells in vitro by blocking the cell cycle at the G2/M phase,which reveals the potential of lotus root polysaccharide in the treatment of ovarian cancer.
文摘BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.
文摘Background: The etiology of ovarian cancer is not well-understood;numerous metabolomics profiling, epidemiological, and hospital-based case control studies have associated abnormal levels of blood glucose and serum lipids with the risk and the prognosis of various types of cancers including ovarian cancer. The association between the risk of the incidence of ovarian cancer and the alterations in the levels of blood glucose and serum lipids is not well defined. Objective: In this study we aimed to compare the levels of blood glucose, triacylglycerols, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with different stages of ovarian cancer and healthy controls to determine how they relate to the risk and prognosis of ovarian cancer. Methodology: In a case-control cross sectional study, we enrolled ninety-nine Sudanese women, diagnosed with ovarian cancer but had not received any kind of treatment as the study group, and a control group of forty-one age-matched, apparently healthy women. The patients were classified according to the International Federation of Obstetricians and Gynecologists staging system into two groups: early stages (stage I & II) and late stages (stages III & IV). Blood glucose and serum lipids;triacylglycerols, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were determined by enzymatic colorimetric methods using commercially available analytical kits. The IBM SPSS version 20 software was used for statistical analysis. A Mann-Whitney U test was used for comparison of the median concentrations of blood glucose, triacylglycerols, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the study groups. Logistic regression model was used to estimate the relative risk of ovarian cancer in relation to levels of blood glucose and serum lipids. P value of 0.05 was considered significant. Results: Our data indicated significantly higher levels of blood glucose (p < 0.001), triacylglycerols (p = 0.002), and low-density lipoprotein cholesterol (p < 0.001), and lower levels of high-density lipoprotein cholesterol (p = 0.023), in ovarian cancer patients compared to the control subjects. No significant difference was found in the levels of blood glucose or any of the serum lipids between patients in the early stages (stage I & II) and those in late stages (stage III & IV) of ovarian cancer. The logistic regression analysis indicated significant association between the elevated levels of the blood glucose, triacylglycerols and low-density lipoprotein cholesterol and the risk of the ovarian cancer. Conclusion: We conclude that the levels of blood glucose, triacylglycerols, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol differ significantly between ovarian cancer patients and the healthy control subjects. The risk of ovarian cancer was positively associated with the levels of blood glucose, triacylglycerols and low-density lipoprotein cholesterol, and negatively associated with levels of high-density lipoprotein cholesterol. Therefore, determination of blood glucose and serum lipids, particularly, triacylglycerols, low-density lipoprotein cholesterol may be helpful as diagnostic indicators of ovarian cancer (OC).
文摘Ovarian cancer (OC) is the most fatal gynecological malignancy, and identifying reliable prognostic indicators can help guide therapeutic treatment. Various tumor marker-guided treatment regimens can considerably improve patient prognosis with a better understanding of the molecular underpinnings of ovarian cancer recurrence and metastasis. Fluorine-18-fluorodeoxyglucose Positron emission tomography/computed tomography (18F-FDG PET/CT) is a molecular imaging tool that provides anatomical and functional information about the tumor, and its volume-based metabolic parameters allow for quantifiable observation of ovarian cancer recurrence, prognosis, and therapeutic efficacy. The combined utilization of serological and radiologic markers has been found to provide increased clinical benefit. This article reviewed the predictive value of serum tumor markers and 18F-FDG PET/CT volumetric metabolic parameters for the prognosis of patients with ovarian cancer.
文摘Ovarian cancer mostly presents with extensive peritoneal cavity and extraperitoneal dissemination. Satisfactory and complete resection of the lesions is one of the key factors to improve the prognosis. The trend of surgical resection of extra-ovarian tissues and organs invaded by the tumor has become obvious in order to remove all primary loci and all metastases as much as possible to minimize residual tumor lesions. This article provides a literature review on organ resection in ovarian cancer cytoreduction, summarizing the perioperative complications and survival outcomes at the time of different organ surgery, with the aim of providing guidance for clinical work.
文摘Ovarian cancer is one of the three major malignant tumors in gynecology, with increasing incidence and mortality rates. Currently, the main treatment methods remain surgical intervention in combination with chemotherapy. However, due to its high recurrence rate and the risk of drug resistance, the overall prognosis is poor. Ovarian cancer has been identified as an immunegenic tumor, and in recent years, with the continued advancement of research into immune evasion mechanisms, immunotherapy has emerged as a groundbreaking treatment modality. This article will focus on the immune escape mechanisms and their application in ovarian cancer, providing a comprehensive overview of its current status and the challenges it faces.
