Dataset Information

E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.

ABSTRACT: E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we investigated the distinct expression and prognostic value of E2Fs in patients with OC by analyzing a series of databases, including ONCOMINE, GEPIA, cBioPortal, Metascape, and Kaplan-Meier plotter. The mRNA expression levels of E2F1/3/5/8 were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC. Aberrant expression of E2F2/5/7/8 was found to be associated with the clinical outcomes of patients with OC. These results suggest that E2F2/5/8 might serve as potential prognostic biomarkers and targets for OC. However, future studies are required to validate our findings and promote the clinical utility of E2Fs in OC.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC6439355 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.

Zhou Quan Q Zhang Fan F He Ze Z Zuo Man-Zhen MZ

Frontiers in oncology 20190322

E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we inves ...[more]

PMID: 30967995

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Project description:BackgroundAutophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression. Phosphorylation of ATG4B is crucial for activation of its protease activity. However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).MethodsThe ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays.ResultsATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells.ConclusionsOur results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.

Project description:BackgroundOvarian cancer is a common gynecological malignant tumor that greatly threatens women's health, so we screened potential biomarkers of ovarian cancer and analyzed their prognostic value.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the ovarian cancer-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of ovarian cancer-related genes. The survival-related genes were screened out through the least absolute shrinkage and selection operator (LASSO) method. Multivariate Cox regression model and stepwise regression analysis were performed to construct the risk model. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to evaluate the prediction accuracy of risk score model. Finally, gene set enrichment analysis (GSEA) and immune cell infiltration analysis were performed to investigate the biological function and immune cell infiltration.ResultsA total of 111 genes were found to have common effects on survival. These genes were mainly involved in metabolism, protein phosphorylation and immune-related signaling pathways. Seven risk genes (AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1, ZNF426) were screened out. Among these genes, AP3D1 and LRFN4 are risk genes and DCAF10, FBXO16, PTPN2, SAYSD1, and ZNF426 are protective genes. These findings suggest that risk status may be an independent prognostic factor. The risk score had a high predictive value for the prognosis of ovarian cancer. In addition, GSEA revealed that the biological function of genes expressed in patients at a high risk was mostly related to immune-related function. The contents of CD4+ T cells, macrophages, myeloid dendritic cells (mDC) and neutrophils were high in samples at a high risk for ovarian cancer.ConclusionsThe abnormal expression of AP3D1, DCAF10, FBXO16, LRFN4, PTPN2, SAYSD1 and ZNF426 is highly related to the progression of ovarian cancer. These seven genes can be used as independent prognostic markers of ovarian cancer. This study not only adds evidence to the pathogenesis of ovarian cancer but also provides scientific basis for judging the prognosis of ovarian cancer.

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E2F2/5/8 Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.

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<i>E2F2/5/8</i> Serve as Potential Prognostic Biomarkers and Targets for Human Ovarian Cancer.

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