Dataset Information

Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma.

ABSTRACT: Increasing evidence has highlighted the important roles of dysregulated long non-coding RNA (lncRNA) expression in tumorigenesis, tumor progression and metastasis. However, lncRNA expression patterns and their prognostic value for tumor relapse in lung adenocarcinoma (LUAD) patients have not been systematically elucidated. In this study, we evaluated lncRNA expression profiles by repurposing the publicly available microarray expression profiles from a large cohort of LUAD patients and identified specific lncRNA signature closely associated with tumor relapse in LUAD from significantly altered lncRNAs using the weighted voting algorithm and cross-validation strategy, which was able to discriminate between relapsed and non-relapsed LUAD patients with sensitivity of 90.9% and specificity of 81.8%. From the discovery dataset, we developed a risk score model represented by the nine relapse-related lncRNAs for prognosis prediction, which classified patients into high-risk and low-risk subgroups with significantly different recurrence-free survival (HR=45.728, 95% CI=6.241-335.1; p=1.69e-04). The prognostic value of this relapse-related lncRNA signature was confirmed in the testing dataset and other two independent datasets. Multivariable Cox regression analysis and stratified analysis showed that the relapse-related lncRNA signature was independent of other clinical variables. Integrative in silico functional analysis suggested that these nine relapse-related lncRNAs revealed biological relevance to disease relapse, such as cell cycle, DNA repair and damage and cell death. Our study demonstrated that the relapse-related lncRNA signature may not only help to identify LUAD patients at high risk of relapse benefiting from adjuvant therapy but also could provide novel insights into the understanding of molecular mechanism of recurrent disease.

SUBMITTER: Zhou M

PROVIDER: S-EPMC5045428 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma.

Zhou Meng M Xu Wanying W Yue Xiaolong X Zhao Hengqiang H Wang Zhenzhen Z Shi Hongbo H Cheng Liang L Sun Jie J

Oncotarget 20160501 20

Increasing evidence has highlighted the important roles of dysregulated long non-coding RNA (lncRNA) expression in tumorigenesis, tumor progression and metastasis. However, lncRNA expression patterns and their prognostic value for tumor relapse in lung adenocarcinoma (LUAD) patients have not been systematically elucidated. In this study, we evaluated lncRNA expression profiles by repurposing the publicly available microarray expression profiles from a large cohort of LUAD patients and identified ...[more]

PMID: 27105492

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Project description:PurposeColon adenocarcinoma (COAD) is the most common type of colorectal cancer (CRC) and is associated with poor prognosis. Emerging evidence has demonstrated that glycosylation by long noncoding RNAs (lncRNAs) was associated with COAD progression. To date, however, the prognostic values of glycosyltransferase (GT)-related lncRNAs in COAD are still largely unknown.MethodsWe obtained the expression matrix of mRNAs and lncRNAs in COAD from The Cancer Genome Atlas (TCGA) database. Then, the univariate Cox regression analysis was conducted to identify 33 prognostic GT-related lncRNAs. Subsequently, LASSO and multivariate Cox regression analysis were performed, and 7 of 33 GT-related lncRNAs were selected to conduct a risk model. Gene set enrichment analysis (GSEA) was used to analyze gene signaling pathway enrichment of the risk model. ImmuCellAI, an online tool for estimating the abundance of immune cells, and correlation analysis were used to explore the tumor-infiltrating immune cells in COAD. Finally, the expression levels of seven lncRNAs were detected in colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsA total of 1,140 GT-related lncRNAs were identified, and 7 COAD-specific GT-related lncRNAs (LINC02381, MIR210HG, AC009237.14, AC105219.1, ZEB1-AS1, AC002310.1, and AC020558.2) were selected to conduct a risk model. Patients were divided into high- and low-risk groups based on the median of risk score. The prognosis of the high-risk group was worse than that of the low-risk group, indicating the good reliability and specificity of our risk model. Additionally, a nomogram based on the risk score and clinical traits was built to help clinical decisions. GSEA showed that the risk model was significantly enriched in metabolism-related pathways. Immune infiltration analysis revealed that five types of immune cells were significantly different between groups, and two types of immune cells were negatively correlated with the risk score. Besides, we found that the expression levels of these seven lncRNAs in tumor cells were significantly higher than those in normal cells, which verified the feasibility of the risk model.ConclusionThe efficient risk model based on seven GT-related lncRNAs has prognostic potential for COAD, which may be novel biomarkers and therapeutic targets for COAD patients.

Project description:BackgroundCuproptosis or copper-dependent cell death is a newly identified non-apoptotic cell death pathway which plays a critical role in the development of multiple cancers. Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators of programmed cell death and lung adenocarcinoma (LUAD) development, and a comprehensive understanding of cuproptosis-related lncRNAs may improve prognosis prediction of LUAD. However, few studies have explored the association of cuproptosis-related lncRNAs with the prognosis of LUAD.MethodsThe RNA sequencing data and corresponding clinical information of patients were extracted from The Cancer Genome Atlas (TCGA) database. Five hundred LUAD patients were randomly divided into a training (n=250) and a testing cohort (n=250). Pearson correlations were performed to identify cuproptosis-related lncRNAs, and univariate Cox regression was performed to screen prognostic lncRNAs. A cuproptosis-related lncRNAs prognostic signature (CLPS) was constructed by the least absolute shrinkage and selection operator Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and multivariate Cox regression were performed to verify the prognostic performance of CLPS. Additionally, immune cell infiltration was estimated using the single-sample gene-set enrichment analysis. pRRophetic algorithm and Tumor Immune Dysfunction and Exclusion algorithm were used to assess the immunotherapy and chemotherapy response, respectively.ResultsCLPS was established based on 61 cuproptosis-related prognostic lncRNAs and exhibited a satisfactory performance predicting LUAD patients' survival (area under the curve at 1, 3, 5 years was 0.784, 0.749, 0.775, respectively). multivariate Cox analysis confirmed the independent prognostic effect of CLPS (hazard ratio: 1.128; 95% confidence interval: 1.071-1.189; P<0.001), and a nomogram containing it exhibited robust validity in prognostic prediction. We further demonstrated a higher CLPS-risk score was associated with lower levels of signatures including immune cell infiltration, immune activation, and immune checkpoints.ConclusionsThe CLPS serves as an effective predictor for the prognosis and therapeutic responses of LUAD patients. Our findings provide promising novel biomarkers and therapeutic targets for LUAD.

Project description:BackgroundCancer growth is significantly influenced by processes such as pyroptosis, apoptosis, and necroptosis that underlie PANoptosis, a proinflammatory programmed cell death. Several studies have examined the long non-coding RNAs (lncRNAs) associated with pancreatic adenocarcinoma (PAAD). However, the predictive value of lncRNAs related to PANoptosis for PAAD has not been established.MethodsThe Clinical Genome Atlas database was used to obtain the transcriptome 、clinical data and the corresponding mutation data of the patients with PAAD in this study. The least absolute shrinkage and selection operator regression analysis was employed to obtain prognosis-related lncRNAs for constructing a risk signature. According to the median risk score of the signature, patients with PAAD were grouped into low- and high-risk groups to further compare the survival prognosis of different risk groups. Time-dependent receiver operating characteristic curves, c-index analysis, nomograms, principal component analysis and univariate Cox and multivariate Cox regression were performed for the internal validation of the signature. In addition, enrichment analysis of different genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Lastly, differences in tumor mutation burden (TMB), immune function, tumor immune dysfunction and rejection (TIDE), and drug response were determined for the two risk groups.ResultsThe signature was constructed with six PANoptosis-related lncRNAs (AC067817.2、LINC02004、AC243829.1、AC092171.5、AP005233.2、AC004687.1) that predicted the prognosis of the patients with PAAD. Survival curves showed that patients in the two risk groups had statistically significant differences in prognosis (P < 0.05), and multi-cox regression analysis identified risk score as an independent risk factor for PAAD prognosis, and internal validation of nomograms showed high confidence in the signature. GO and KEGG enrichment analysis showed functional and pathway differences between the high- and low-risk groups. TMB evaluation demonstrated that patients in the high-risk group had a higher frequency of mutations. The TIDE score indicated that the high-risk group had a lower risk of immunotherapy escape and better immunotherapy outcomes. Additionally, the two risk groups revealed significantly different responses to 11 anticancer drugs.ConclusionWe identified a novel risk signature for PANoptosis-related lncRNAs, which is a standalone prognostic indicator for PAAD. The PANoptosis-related lncRNA risk signature may be relevant for immunotherapy and a therapeutic target for PAAD.

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Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma.

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Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma.

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