Dataset Information

Identification of long non-coding RNAs biomarkers associated with progression of endometrial carcinoma and patient outcomes.

ABSTRACT: Endometrial carcinoma is a complex disease characterized by both genetic, epigenetic and environmental factors. Increasing evidence has suggested that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers. In this study, we performed a comparison analysis for lncRNA expression between patients with early-stage (stage I/II) and those with advanced-stage (stage III/IV) derived from The Cancer Genome Atlas (TCGA) project and identified 17 differentially expressed lncRNAs using student t-test. Five of the 17 differentially expressed lncRNAs were selected as optimal biomarkers that are significantly associated with progression of UCEC using random forest feature selection procedure. A risk classifier of five lncRNAs was developed to as a molecular signature that identifies patients at high risk for progression using support vector machine. Results of five-lncRNA risk classifier achieved high discriminatory performance in distinguishing advanced stage from early stage with 78% prediction accuracy, 96.6% sensitivity and 76.6% specificity. Functional analysis suggested that these five lncRNA biomarkers may play critical roles in the progression of UCEC by participating in important cancer-related biological processes. Our study will help to improve our understanding of underlying mechanisms in the progression of UCEC and provide novel lncRNAs as candidate predictive biomarkers for the identification of patients with high risk for progression.

SUBMITTER: Sun Y

PROVIDER: S-EPMC5581054 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Identification of long non-coding RNAs biomarkers associated with progression of endometrial carcinoma and patient outcomes.

Sun Yanan Y Zou Xiaoyan X He Jun J Mao Yuqin Y

Oncotarget 20170430 32

Endometrial carcinoma is a complex disease characterized by both genetic, epigenetic and environmental factors. Increasing evidence has suggested that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers. In this study, we performed a comparison analysis for lncRNA expression between patients with early-stage (stage I/II) and those with advanced-stage (stage III/IV) derived from The Cancer Genome Atlas (TCGA) project and identified 17 differentially e ...[more]

PMID: 28881755

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Project description:The aim of the present study was to identify long non-coding RNA (lncRNA)-based prognostic biomarkers in papillary renal cell carcinoma (pRCC). lncRNA expression data and corresponding clinical data from patients with pRCC were obtained from The Cancer Genome Atlas. R software and packages were used for data analysis. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression were performed to identify key lncRNAs, which were then used to construct a prognostic model using multivariate Cox regression analysis. Patients were divided into high- and low-risk groups, and Kaplan-Meier (KM) survival curves and time-dependent receiver operating characteristic (ROC) curves were plotted. The C-index was calculated to estimate the model's prognostic power. The hazard ratio (HR), 95% confidence interval (CI), and statistical significance of each key lncRNA were also calculated by multivariate Cox regression. Based on the result of the multivariate Cox regression analysis, KM survival plots were plotted for each significantly associated lncRNA. The subcellular locations of the prognostic biomarkers were predicted using lncRNAMap and lncLocator. A total of 17 lncRNA signatures were identified as key lncRNAs. Overall survival rate was significantly higher in the low-risk group compared with the high-risk group. The areas under the ROC curve were 0.93 (3-year ROC) and 0.902 (5-year ROC), and the C-index was 0.915. A forest plot was used to illustrate the HR and 95% CI of key lncRNAs. KM survival analysis revealed the prognostic significance of two protective biomarkers, AC024022.1 and GAS6-AS1, and three adverse biomarkers, AC087379.2, AL352984.1, and AL499627.1. It was predicted that AC024022.1 and AC087379.2 may be located in the cytoplasm and GAS6-AS1 may be located in the cytosol. The present study may contribute to the management of pRCC and serve as a foundation for further investigations into the underlying mechanism of tumorigenesis and progression of pRCC.

Project description:Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, due to poor diagnosis and treatment. There is increasing evidence that demonstrates the involvement of long non-coding RNAs (lncRNAs) in carcinogenesis and cancer progression. Therefore, the aim of the present study was to explore potential lncRNA-associated features of patients with OSCC as a valuable and independent prognostic biomarker. A total of 268 lncRNA expression profiles and clinical patient information on OSCC were downloaded from The Cancer Genome Atlas database. The clinical information was exploited for prescreening, using Cox regression analysis, and differentially expressed lncRNAs (DElncRNAs) were identified using edgeR software. Using the 'caret' package, the datasets were categorized into test datasets and training datasets, respectively. Through bioinformatics, seven prognostic DElncRNAs were selected. Using the regression coefficients, a risk score based on the seven-DElncRNA signature was developed to assess the prognostic function of key DElncRNAs. According to the median risk score, patients were classified into high-risk and low-risk groups in the training and test datasets. Additionally, receiver operating characteristic (ROC) curve analysis was conducted to evaluate the sensitivity and specificity of the prognostic DElncRNAs, and the optimal cut-off point was obtained from ROC analysis. Based on the optimal cut-off point, the patients were also categorized into high-risk and low-risk groups. Notably, the optimal cut-off point was more sensitive than the median risk score, particularly in the test dataset. The Kaplan-Meier survival and log rank test analysis results indicated that the P-value, based on the optimal cut-off, was less than the median risk cut-off. Additionally, stratified analysis results revealed that the seven-DElncRNAs signature was also independent of OSCC age. Furthermore, the findings of the present study suggested that the seven-DElncRNA signature can be used as a potential prognostic indicator and may have important clinical significance in OSCC.

Dataset Information

Identification of long non-coding RNAs biomarkers associated with progression of endometrial carcinoma and patient outcomes.

Publications

Identification of long non-coding RNAs biomarkers associated with progression of endometrial carcinoma and patient outcomes.

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