J Cancer 2020; 11(7):1940-1948. doi:10.7150/jca.37003 This issue

Research Paper

Development and validation of a 4-gene combination for the prognostication in lung adenocarcinoma patients

Xiao-Hong Yin1,2, Li-Ping Yu2, Xiao-Hong Zhao2, Qin-Mei Li3, Xiao-Ping Liu4✉, Li He1✉

1. Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei province, China
2. Wuhan University School of Health Sciences, Wuhan, Hubei province, China
3. Department of Epidemiology, Department of Epidemiology, School of Health Sciences, Wuhan University, Wuhan, Hubei, China
4. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei province, China

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Citation:
Yin XH, Yu LP, Zhao XH, Li QM, Liu XP, He L. Development and validation of a 4-gene combination for the prognostication in lung adenocarcinoma patients. J Cancer 2020; 11(7):1940-1948. doi:10.7150/jca.37003. Available from https://www.jcancer.org/v11p1940.htm

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Abstract

Objective: To identify a multi-gene prognostic factor in patients with lung adenocarcinoma (LUAD).

Materials and methods Prognosis-related genes were screened in the TCGA-LUAD cohort. Then, patients in this cohort were randomly separated into training set and test set. Least absolute shrinkage and selection operator (LASSO) regression was performed to the penalized the Cox proportional hazards regression (CPH) model on the training set, and a prognostication combination based on the result of LASSO analysis was developed. By performing Kaplan-Meier curve analysis, univariate and multivariable CPH model on the overall survival (OS) as well as recurrence free survival (RFS), the prognostication performance of the multigene combination were evaluated. Moreover, we constructed a nomogram and performed decision curve analysis to evaluate the clinical application of the multigene combination.

Results We obtained 99 prognosis-related genes and screened out a 4-gene combination (including CIDEC, ZFP3, DKK1, and USP4) according to the LASSO analysis. The results of survival analyses suggested that patients in the 4-gene combination low-risk group had better OS and RFS than those in the 4-gene combination high-risk group. The 4-gene mentioned was demonstrated to be independent prognostic factor of patients with LUAD in the training set(OS, HR=11.962, P<0.001; RFS, HR=9.281, P<0.001) and test set (OS, HR=5.377, P=0.003; RFS, HR=2.949, P=0.104). More importantly, its prognosis performance was well in the validation set (OS, HR=0.955, P=0.002; RFS, HR=1.042, P<0.001).

Conclusions We introduced a 4-gene combination which could predict the survival of LUAD patients and might be an independent prognostic factor in LUAD.

Keywords: lung adenocarcinoma, prognostication, least absolute shrinkage and selection operator, survival analysis