Prognostic Signature for Lung Adenocarcinoma Patients Based on Cell-Cycle-Related Genes

Wei Jiang; Jiameng Xu; Zirui Liao; Guangbin Li; Chengpeng Zhang; Yu Feng

doi:10.3389/fcell.2021.655950

Prognostic Signature for Lung Adenocarcinoma Patients Based on Cell-Cycle-Related Genes

Front Cell Dev Biol. 2021 Mar 18:9:655950. doi: 10.3389/fcell.2021.655950. eCollection 2021.

Authors

Wei Jiang¹, Jiameng Xu², Zirui Liao³, Guangbin Li¹, Chengpeng Zhang¹, Yu Feng¹

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
³ Medical College, Orthopedic Institute, Soochow University, Suzhou, China.

Abstract

Objective: To screen lung adenocarcinoma (LUAC)-specific cell-cycle-related genes (CCRGs) and develop a prognostic signature for patients with LUAC.

Methods: The GSE68465, GSE42127, and GSE30219 data sets were downloaded from the GEO database. Single-sample gene set enrichment analysis was used to calculate the cell cycle enrichment of each sample in GSE68465 to identify CCRGs in LUAC. The differential CCRGs compared with LUAC data from The Cancer Genome Atlas were determined. The genetic data from GSE68465 were divided into an internal training group and a test group at a ratio of 1:1, and GSE42127 and GSE30219 were defined as external test groups. In addition, we combined LASSO (least absolute shrinkage and selection operator) and Cox regression analysis with the clinical information of the internal training group to construct a CCRG risk scoring model. Samples were divided into high- and low-risk groups according to the resulting risk values, and internal and external test sets were used to prove the validity of the signature. A nomogram evaluation model was used to predict prognosis. The CPTAC and HPA databases were chosen to verify the protein expression of CCRGs.

Results: We identified 10 LUAC-specific CCRGs (PKMYT1, ETF1, ECT2, BUB1B, RECQL4, TFRC, COCH, TUBB2B, PITX1, and CDC6) and constructed a model using the internal training group. Based on this model, LUAC patients were divided into high- and low-risk groups for further validation. Time-dependent receiver operating characteristic and Cox regression analyses suggested that the signature could precisely predict the prognosis of LUAC patients. Results obtained with CPTAC, HPA, and IHC supported significant dysregulation of these CCRGs in LUAC tissues.

Conclusion: This prognostic prediction signature based on CCRGs could help to evaluate the prognosis of LUAC patients. The 10 LUAC-specific CCRGs could be used as prognostic markers of LUAC.

Keywords: GEO; cell cycle-related genes; lung adenocarcinoma; overall survival; prognostic signature.