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Identification of seven-gene signature for prediction of lung squamous cell carcinoma

Authors Wang Z, Wang Z, Niu X, Liu J, Wang Z, Chen L, Qin B

Received 20 December 2018

Accepted for publication 13 April 2019

Published 24 July 2019 Volume 2019:12 Pages 5979—5988

DOI https://doi.org/10.2147/OTT.S198998

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Zhe Wang,1,* Zhongmiao Wang,1,* Xing Niu,2 Jie Liu,3 Zhuning Wang,2 Lijie Chen,4 Baoli Qin1

1Department of Gastrointestinal Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, People’s Republic of China; 2Department of Second Clinical College, Shengjing Hospital affiliated to China Medical University, Shenyang 110004, Liaoning Province, People’s Republic of China; 3Science Experiment Center of China Medical University, China Medical University, Shenyang 110122, Liaoning Province, People’s Republic of China; 4Department of Third Clinical College, China Medical University, Shenyang 110122, Liaoning Province, People’s Republic of China

*These authors contributed equally to this work

Background and aim: Lung squamous cell carcinoma (LUSC), is a pathological subtype of lung cancer, accounting for 30% of the lung cancers. A reliable model was constructed, based on the whole gene expression profiles, to predict the prognosis of patients with LUSC.
Methods: The RNA-Seq data of LUSC was downloaded from the TCGA database, and differentially expressed genes (p<0.05, |log2fold change| >1) were screened out. By univariate and multivariate Cox regression analysis, we identified seven prognosis-related genes. Then, we established a risk score staging system to predict the prognosis of patients with LUSC. Compared with other clinical parameters, the risk score was an independent prognostic factor and had a better performance in predicting prognosis. Finally, GSEA analysis was carried out to determine the enrichment pathway significantly. The risk score models were established by Cox proportional hazard regression analysis; the ROC curve was applied to test the performance of risk score model. All the statistical analysis was accomplished by R packages.
Results: In this study, a model was constructed to predict prognosis, which contains seven genes: CSRNP1, CLEC18B, MIR27A, AC130456.4, DEFA6, ARL14EPL, and ZFP42. Based on the model, the risk score of each patient was calculated with LUSC (hazard ratio [HR]=2.673, 95% CI=1.871–3.525). It was found that the risk score can distinguish high-risk and low-risk groups in prognosis of LUSC patients, independently. Furthermore, the model was validated by ROC curves in the testing dataset and the whole dataset. Lastly, by gene set enrichment analysis (GSEA), we showed the main enrichment pathways were DNA damage stimulus, DNA repair, and DNA replication. It was suggested that the risk score may provide a new and reliable method for prognosis prediction.
Conclusion: The results of this study suggested that the risk score based on seven-genes could indicate a promising and independent prognostic biomarker for LUSC patients.

Keywords: lung squamous cell carcinoma, prognosis, gene set enrichment analysis, Cox regression model, risk score


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