Int J Biol Sci 2020; 16(5):869-881. doi:10.7150/ijbs.38846

Research Paper

Prognostic values of a novel multi-mRNA signature for predicting relapse of cholangiocarcinoma

Han Guo1*, Jie Cai1*, Xuan Wang2*, Bingrui Wang1, Fang Wang2, Xiang Li1, Xiaoye Qu1, Xianming Kong4, Yueqiu Gao2, Hailong Wu3, Xuehua Sun2✉, Qiang Xia1✉, Xiaoni Kong1,2✉

1. Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2. Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
3. Shanghai Key Laboratory for Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine and Health Sciences, Shanghai, China.
4. Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
* These authors contribute equally to this work.

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Citation:
Guo H, Cai J, Wang X, Wang B, Wang F, Li X, Qu X, Kong X, Gao Y, Wu H, Sun X, Xia Q, Kong X. Prognostic values of a novel multi-mRNA signature for predicting relapse of cholangiocarcinoma. Int J Biol Sci 2020; 16(5):869-881. doi:10.7150/ijbs.38846. Available from http://www.ijbs.com/v16p0869.htm

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Abstract

Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database. The Least absolute shrinkage and selection operator (LASSO) regression model was used to establish a 7-mRNA-based signature that was significantly related to the recurrence-free survival (RFS) in two test series. Based on the 7-mRNA signature, the cohort TCGA patients could be divided into high-risk or low-risk subgroups with significantly different RFS [p < 0.001, hazard ratio (HR): 48.886, 95% confidence interval (CI): 6.226-3.837E+02]. Simultaneously, the prognostic value of the 7-mRNA signature was confirmed in clinical samples of Ren Ji hospital (p < 0.001, HR: 4.558, 95% CI: 1.829-11.357). Further analysis including multivariable and sub-group analyses revealed that the 7-mRNA signature was an independent prognostic value for recurrence of patients with CCA. In conclusion, our results might provide an efficient tool for relapse prediction and were beneficial to individualized management for CCA patients.

Keywords: cholangiocarcinoma, Gene Expression Omnibus database, least absolute shrinkage and selection operator model, mRNA signature, recurrence-free survival.