Identification of seven-gene marker to predict the survival of patients with lung adenocarcinoma using integrated multi-omics data analysis.

Abstract

BackgroundThe mechanism of cancer occurrence and development could be understood with multi‐omics data analysis. Discovering genetic markers is highly necessary for predicting clinical outcome of lung adenocarcinoma (LUAD).MethodsClinical follow‐up information, copy number variation (CNV) data, single nucleotide polymorphism (SNP), and RNA‐Seq were acquired from The Cancer Genome Atlas (TCGA). To obtain robust biomarkers, prognostic‐related genes, genes with SNP variation, and copy number differential genes in the training set were selected and further subjected to feature selection using random forests. Finally, a gene‐based prediction model for LUAD was validated in validation datasets.ResultsThe study filtered 2071 prognostic‐related genes and 230 genomic variants, 1878 copy deletions, and 438 significant mutations. 218 candidate genes were screened through integrating genomic variation genes and prognosis‐related genes. 7 characteristic genes (RHOV, CSMD3, FBN2, MAGEL2, SMIM4, BCKDHB, and GANC) were identified by random forest feature selection, and many genes were found to be tumor progression‐related. A 7‐gene signature constructed by Cox regression analysis was an independent prognostic factor for LUAD patients, and at the same time a risk factor in the test set, external validation set, and training set. Noticeably, the 5‐year AUC of survival in the validation set and training set was all ˃ 0.67. Similar results were obtained from multi‐omics validation datasets.ConclusionsThe study builds a novel 7‐gene signature as a prognostic marker for the survival prediction of patients with LUAD. The current findings provided a set of new prognostic and diagnostic biomarkers and therapeutic targets.