Identifying a 6-Gene Prognostic Signature for Lung Adenocarcinoma Based on Copy Number Variation and Gene Expression Data

Abstract

The occurrence of lung adenocarcinoma (LUAD) is a complicated process, involving the genetic and epigenetic changes of proto-oncogenes and oncogenes. The objective of this study was to establish new predictive signatures of lung adenocarcinoma based on copy number variations (CNVs) and gene expression data. Next-generation sequencing was implemented to obtain gene expression and CNV information. According to univariate, multivariate survival Cox regression analysis, and LASSO analysis, the expression profiles of lung adenocarcinoma patients were screened and a risk score formula was established and experimentally validated in a local cohort. The model was evaluated by three independent cohorts (TCGA-LUAD, GSE31210, and GSE30219), and then validated by clinical samples from LUAD patients. A total of 844 CNV-related differentially expressed genes (CNV-related DEGs) were identified. These genes are significantly associated with the imbalance of various oxidative stress pathways. A CNV-associated-six gene signature was dramatically linked to overall survival in lung adenocarcinoma samples from both training and validation groups. Functional enrichment analysis further revealed involvement of genes in p53 signaling pathway and cell cycle as well as the mismatch repair pathway. Risk score is an independent marker considering clinical parameters and had better prediction in clinical subpopulation. The same signature also classified tumor tissues of clinical patients with CNV detected from their corresponding nontumorous tissues with an accuracy of 0.92. In conclusion, we identified a new class of 6 CNV-related gene markers that may act as efficient prognostic predictors of lung adenocarcinoma, thus contributing to individualized treatment decisions in patients.

Identification and validation of a novel anoikis-related prognostic model for prostate cancer

“…ABCC5 is a member of the ATP-binding cassette transporter family, and its overexpression has been linked to multidrug resistance in cancer (Li et al, 2018a;Zhang et al, 2018). Finally, TPSB2 is a serine protease that has been linked to the development of several cancers (Huang et al, 2022;Morikawa et al, 2018). In conclusion, the identi cation of these four genes and the development of the anoikis-related signature provide a potential prognostic tool for the prediction of PCa patient survival.…”

Identification and validation of a novel anoikis‐related prognostic model for prostate cancer

“…ABCC5 is a member of the ATP‐binding cassette transporter family, and its overexpression has been linked to multidrug resistance in cancer (Li, Gu, et al., 2018 ; Zhang et al., 2018 ). Finally, TPSB2 is a serine protease that has been linked to the development of several cancers (Huang et al., 2022 ; Morikawa et al., 2018 ). These genes also provide potential targets for developing novel therapeutics for PCa.…”

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

“…The accuracy of the nomogram was validated by calibration, ROC, and decision curves (DCA) using “ggDCA” and “survival” package, respectively. Furthermore, to test the superiority of the risk model, we compared our risk score with other signature, including Wang et al [ 19 ], Jiang et al [ 20 ], Deng et al [ 21 ], Huang et al [ 22 ], and Li et al [ 23 ]. The “survcomp” package was used to assess index of concordance (C-index) and RMS.…”