Computational detection of a genome instability-derived lncRNA signature for predicting the clinical outcome of lung adenocarcinoma

Abstract

Evidence has been emerging of the importance of long non-coding RNAs (lncRNAs) in genome instability. However, no study has established how to classify such lncRNAs linked to genomic instability, and whether that connection poses a therapeutic significance. Here, we established a computational frame derived from mutator hypothesis by combining profiles of lncRNA expression and those of somatic mutations in a tumor genome, and identified 185 candidate lncRNAs associated with genomic instability in lung adenocarcinoma (LUAD). Through further studies, we established a six lncRNA-based signature, which assigned patients to the high- and low-risk groups with different prognosis. Further validation of this signature was performed in a number of separate cohorts of LUAD patients. In addition, the signature was found closely linked to genomic mutation rates in patients, indicating it could be a useful way to quantify genomic instability. In summary, this research offered a novel method by through which more studies may explore the function of lncRNAs and presented a possible new way for detecting biomarkers associated with genomic instability in cancers.

Keywords: genome instability; long non-coding RNAs; lung adenocarcinoma; mutator phenotype.