Dataset Information

Identification of a multidimensional transcriptome prognostic signature for lung adenocarcinoma.

ABSTRACT: BACKGROUND:Lung adenocarcinoma (LUAD) is one of the leading contributors to cancer-related deaths worldwide. The objective of the current study is to identify a multidimensional transcriptome prognostic signature by combining protein-coding gene (PCG) with long non-coding RNA (lncRNA) for patients with LUAD. METHODS:We obtained LUAD PCG and lncRNA expression profile data from three datasets in the Gene Expression Omnibus database and conducted survival analyzes for these individuals. RESULTS:We established a predictive model comprising the three PCGs (NHLRC2, PLIN5, GNAI3), and one lncRNA (AC087521.1). This model segregated patients with LUAD into low- and high-risk groups based on significant differences in survival in the training dataset (GSE31210, n = 226, log-rank test P < .001). Risk stratification of the model was subsequently validated in other two test datasets (GSE37745, n = 106, log-rank test P < .001; GSE30219, n = 85, log-rank test P = .006). Time-dependent receiver operating characteristic (timeROC) curve analysis demonstrated that the model correlated strongly with disease progression and outperformed pathological stage in terms of prognostic ability. Cox proportional hazards regression analysis revealed that the signature could serve as an independent predictor of clinical outcomes in patients with LUAD. CONCLUSIONS:We describe a novel multidimensional transcriptome signature that can predict survival probabilities in patients with LUAD.

SUBMITTER: Ye J

PROVIDER: S-EPMC6868416 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Identification of a multidimensional transcriptome prognostic signature for lung adenocarcinoma.

Ye Jing J Liu Hui H Xu Zhi-Li ZL Zheng Ling L Liu Rong-Yu RY

Journal of clinical laboratory analysis 20190811 9

<h4>Background</h4>Lung adenocarcinoma (LUAD) is one of the leading contributors to cancer-related deaths worldwide. The objective of the current study is to identify a multidimensional transcriptome prognostic signature by combining protein-coding gene (PCG) with long non-coding RNA (lncRNA) for patients with LUAD.<h4>Methods</h4>We obtained LUAD PCG and lncRNA expression profile data from three datasets in the Gene Expression Omnibus database and conducted survival analyzes for these individua ...[more]

PMID: 31402485

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Project description:Background:Lung cancer has the highest morbidity and mortality worldwide, and lung adenocarcinoma (LADC) is the most common pathological subtype. Accumulating evidence suggests the tumor microenvironment (TME) is correlated with the tumor progress and the patient's outcome. As the major components of TME, the tumor-infiltrated immune cells and stromal cells have attracted more and more attention. In this study, differentially expressed immune and stromal signature genes were used to construct a TME-related prognostic model for predicting the outcomes of LADC patients. Methods:The expression profiles of LADC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) related to the TME of LADC were identified using TCGA dataset by Wilcoxon rank sum test. The prognostic effects of TME-related DEGs were analyzed using univariate Cox regression. Then, the least absolute shrinkage and selection operator (LASSO) regression was performed to reduce the overfit and the number of genes for further analysis. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and GEO datasets, respectively. The Kyoto Encyclopedia of Genes and Genomes analysis of gene signature was performed using Gene Set Enrichment Analysis (GSEA). Finally, the overall immune status, tumor purity and the expression profiles of HLA genes of high- and low-risk samples was further analyzed to reveal the potential mechanisms of prognostic effects of the model. Results:A total of 93 TME-related DEGs were identified, of which 23 DEGs were up-regulated and 70 DEGs were down-regulated. The univariate cox analysis indicated that 23 DEGs has the prognostic effects, the hazard ratio ranged from 0.65 to 1.25 (p < 0.05). Then, seven genes were screened out from the 23 DEGs by LASSO regression method and were further analyzed by step multivariate Cox regression. Finally, a three-gene (ADAM12, Bruton Tyrosine Kinase (BTK), ERG) signature was constructed, and ADAM12, BTK can be used as independent prognostic factors. The three-gene signature well stratified the LADC patients in both training (TCGA) and testing (GEO) datasets as high-risk and low-risk groups, the 3-year area under curve (AUC) of ROC curves of three GEO sets were 0.718 (GSE3141), 0.646 (GSE30219) and 0.643 (GSE50081). The GSEA analysis indicated that highly expressed ADAM12, BTK, ERG mainly correlated with the activation of pathways involving in focal adhesion, immune regulation. The immune analysis indicated that the low-risk group has more immune activities and higher expression of HLA genes than that of the high-risk group. In sum, we identified and constructed a three TME-related DEGs signature, which could be used to predict the prognosis of LADC patients.

Project description:BackgroundCuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients.MethodsRNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB).ResultsWe have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.

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Identification of a multidimensional transcriptome prognostic signature for lung adenocarcinoma.

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Identification of a multidimensional transcriptome prognostic signature for lung adenocarcinoma.

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