Construction and validation of a seven-microRNA signature as a prognostic tool for lung squamous cell carcinoma

Abstract

Objective: The aim of this study was to construct and validate a microRNA (miR)-based signature as a prognostic tool for lung squamous cell carcinoma (LUSC).

Materials and methods: With the use of mature miR expression profiles downloaded from The Cancer Genome Atlas database, we identified differentially expressed miRs between LUSC and matched healthy lung tissue. Thereafter, we carried out an evaluation of the association of differentially expressed miRs with overall survival (OS) with the use of univariate and multivariate Cox regression analysis. This analysis was eventually employed for the construction of a miR-based signature, which effectively predicted the prognosis. The functional enrichment analysis of the miRs included in the signature was used to explore their potential molecular mechanism in LUSC.

Results: A total of 316 miRs were differentially expressed between LUSC and matched healthy lung tissues in the training set. Following the univariate and multivariate Cox regression analysis, we found that seven miRs were independent prognostic factors. Each patient received a signature index ranging from 0 to 7. Patients with LUSC were divided into high-risk, intermediate-risk, and low-risk groups in accordance with their signature index and the OS in the three groups was significantly different. This finding remains consistent in the validation set. Besides that, this seven-miR signature remained an independent prognostic factor in comparison with routine clinicopathologic features. The seven-miR signature is a promising biomarker for predicting the 5-year survival rate of LUSC with an area under the receiver operating characteristic curveof 0.712 in the training set and 0.688 in the validation set, respectively. The target genes of seven miRs may be involved in various pathways associated with lung cancer, for instance the mitogen-activated protein kinase signaling pathway and the Wnt signaling pathway.

Conclusion: Using this signature, patients with LUSC can be divided into high-risk, intermediate-risk, and low-risk groups for more personalized management.

Keywords:

• lung squamous cell carcinoma
• microRNA-based signature
• prognosis

Acknowledgments

This work was supported by the Youth Science Foundation of Guangxi Medical University (Grant number: GXMUYSF 201716) and the Guangxi Natural Science Foundation (Grant number: 2018GXNSFBA281091 and 2018GXNSFAA281091).

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.