Dataset Information

Identification of a five-gene signature for predicting the progression and prognosis of stage I endometrial carcinoma.

ABSTRACT: Uterine corpus endometrial carcinoma (UCEC) is often diagnosed at an early clinical stage based on abnormal vaginal bleeding. However, the prognosis of UCEC is poor. The present study was conducted to identify novel tumor grade-related genes with the potential to predict the prognosis and progression of UCEC. A total of three gene expression microarray datasets were downloaded from the Gene Expression Omnibus database, and one RNA-sequencing dataset with corresponding clinical information of patients with UCEC was obtained from The Cancer Genome Atlas database. In summary, 1,447 differentially expressed genes (DEGs) were identified between endometrial cancerous tissues and normal endometrial tissues. Weighted gene co-expression network analysis was performed to assess the associations between DEGs and clinical traits. In total, five genes were found to be highly associated with the tumorigenesis and prognosis of UCEC. Among them, BUB1 mitotic checkpoint serine/threonine kinase B, cyclin B1, cell-division cycle protein 20 and non-SMC condensing I complex subunit G were involved in cell cycle regulation pathways, and DLG-associated protein 5 was involved in the Notch receptor 3 signaling pathway based on functional enrichment analyses. Of the five genes, four were highly expressed in endometrial cancerous tissues compared with normal endometrial tissues at the protein level. In addition, the higher expression of these genes predicted a higher tumor grade and worse overall survival. In conclusion, the present study revealed a 5-gene signature that can be used to predict the progression of UCEC.

SUBMITTER: Bian J

PROVIDER: S-EPMC7400971 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Identification of a five-gene signature for predicting the progression and prognosis of stage I endometrial carcinoma.

Bian Jia J Xu Yuzi Y Wu Fei F Pan Qiangwei Q Liu Yunlong Y

Oncology letters 20200701 3

Uterine corpus endometrial carcinoma (UCEC) is often diagnosed at an early clinical stage based on abnormal vaginal bleeding. However, the prognosis of UCEC is poor. The present study was conducted to identify novel tumor grade-related genes with the potential to predict the prognosis and progression of UCEC. A total of three gene expression microarray datasets were downloaded from the Gene Expression Omnibus database, and one RNA-sequencing dataset with corresponding clinical information of pat ...[more]

PMID: 32782557

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Project description:BackgroundPTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC.MethodsWe obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve.ResultsThe K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC.ConclusionIn summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.

Project description:BackgroundHepatocellular carcinoma (HCC) is a highly lethal disease. Effective prognostic tools to guide clinical decision-making for HCC patients are lacking.ObjectiveWe aimed to establish a robust prognostic model based on differentially expressed genes (DEGs) in HCC.MethodsUsing datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Genome Consortium (ICGC), DEGs between HCC tissues and adjacent normal tissues were identified. Using TCGA dataset as the training cohort, we applied the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analyses to identify a multi-gene expression signature. Proportional hazard assumptions and multicollinearity among covariates were evaluated while building the model. The ICGC cohort was used for validation. The Pearson test was used to evaluate the correlation between tumor mutational burden and risk score. Through single-sample gene set enrichment analysis, we investigated the role of signature genes in the HCC microenvironment.ResultsA total of 274 DEGs were identified, and a six-DEG prognostic model was developed. Patients were stratified into low- or high-risk groups based on risk scoring by the model. Kaplan-Meier analysis revealed significant differences in overall survival and progression-free interval. Through univariate and multivariate Cox analyses, the model proved to be an independent prognostic factor compared to other clinic-pathological parameters. Time-dependent receiver operating characteristic curve analysis revealed satisfactory prediction of overall survival, but not progression-free interval. Functional enrichment analysis showed that cancer-related pathways were enriched, while immune infiltration analyses differed between the two risk groups. The risk score did not correlate with levels of PD-1, PD-L1, CTLA4, or tumor mutational burden.ConclusionsWe propose a six-gene expression signature that could help to determine HCC patient prognosis. These genes may serve as biomarkers in HCC and support personalized disease management.

Dataset Information

Identification of a five-gene signature for predicting the progression and prognosis of stage I endometrial carcinoma.

Publications

Identification of a five-gene signature for predicting the progression and prognosis of stage I endometrial carcinoma.

Similar Datasets

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