Elastic Net-Based Identification of a Multigene Combination Predicting the Survival of Patients with Cervical Cancer
Hua Wang, Shu-Wei Li, Wei Li, Hong-Bing Cai
Department of Obstetrics and Gynecology, Xiangyang No.1 People’s Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, Hubei, China (mainland)
Med Sci Monit 2019; 25:10105-10113
The objective of the present study was to identify prognostication biomarkers in patients with cervical cancer.
MATERIAL AND METHODS: Survival related genes were identified in The Cancer Genome Atlas (TCGA) cervical cancer study, and they were included into an elastic net regularized Cox proportional hazards regression model (CoxPH). The genes that their coefficients that were not zero were combined to build a prognostication combination. The prognostication performance of the multigene combination was evaluated and validated using Kaplan-Meier curve and univariate and multivariable CoxPH model. Meanwhile, a nomogram was built to translate the multigene combination into clinical application.
RESULTS: There were 37 survival related genes identified, 9 of which were integrated to build a multigene combination. The area under the curve (AUC) of receiver operating characteristic (ROC) curve at 1-year, 3-year, 5-year, and 7-year in the training set were 0.757, 0.744, 0.799, and 0.854, respectively, and the multigene combination could stratify patients into significantly different prognostic groups (hazard ratio [HR]=0.2223, log-rank P<0.0001). Meanwhile, the corresponding AUCs in the test set was 0.767, 0.721, 0.735, and 0.703, respectively, and the multigene combination could classify patients into different risk groups (HR=0.3793, log-rank P=0.0021). The multigene combination could stratify patients with early stage and advanced stage into significantly different survival groups in the training set and test set. The prognostication performance of the multigene combination was better compared with 3 existing prognostic signatures. Finally, a multigene containing nomogram was developed.
CONCLUSIONS: We developed a multigene combination which could be treated as an independent prognostic factor in cervical cancer and be translated into clinical application.
Keywords: Biological Markers, Proportional Hazards Models, Survival Analysis, Uterine Cervical Neoplasms