Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma
| Autor: | De-Ti Peng, Jian-Ping Lai, Yi-Jun Qiu, Wei-Qu Yuan, Dan-Ping Huang, Jing-Jing Tong, Yi-Hao Zeng, Mianmian Liao, Guang-dong Tong |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Genome instability
Male Aging Carcinoma Hepatocellular The Cancer Genome Atlas Computational biology Biology medicine.disease_cause Genome long non-coding RNAs Germline mutation medicine Biomarkers Tumor Humans Aged Neoplasm Staging Mutation Receiver operating characteristic Proportional hazards model Liver Neoplasms Cancer Computational Biology Cell Biology hepatocellular carcinoma Gene signature Middle Aged medicine.disease genomic instability Prognosis Female RNA Long Noncoding prognosis prediction Transcriptome Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, genome instability-associated lncRNAs (GILncRNAs) and their performance in clinical prognostic significance in hepatocellular carcinoma (HCC) are rarely reported. Our study constructed a computational framework integrating somatic mutation information and lncRNA expression profiles of HCC genome and we identified 88 GILncRNAs of HCC. Function enrichment analysis revealed that GILncRNAs were involved in various metabolism processes and genome instability of cancer. A genome instability-derived lncRNA-based gene signature (GILncSig) was constructed using training set data. The performance of GILncSig for outcome prediction was validated in testing set and The Cancer Genome Atlas (TCGA) set. The multivariate cox regression analysis and stratification analysis demonstrated GILncSig could serve as an independent prognostic factor for the overall survival of HCC patients. The time-dependent Receiver Operating Characteristic (ROC) curve illustrated GILncSig outperformed two recently published lncRNA signatures for overall survival prediction. The combination of GILncSig and tumor protein p53 (TP53) mutation status exhibited better prognostic performance in survival evaluation compared to TP53 mutation status alone. AC145343.1 was further validated to be a risk factor for HCC in vitro among GILncSig. Overall, our study provided a novel approach for identification of genome instability-associated lncRNAs and established an independent risk score system for outcome prediction of HCC patients, which provided a new insight for exploring in-depth mechanism and potential therapy strategy. |
| Databáze: | OpenAIRE |
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