Recurrence-Associated Long Non-coding RNA Signature for Determining the Risk of Recurrence in Patients with Colon Cancer

Meng Zhou; Long Hu; Zicheng Zhang; Nan Wu; Jie Sun; Jianzhong Su

doi:10.1016/j.omtn.2018.06.007

Recurrence-Associated Long Non-coding RNA Signature for Determining the Risk of Recurrence in Patients with Colon Cancer

Mol Ther Nucleic Acids. 2018 Sep 7:12:518-529. doi: 10.1016/j.omtn.2018.06.007. Epub 2018 Jun 26.

Authors

Meng Zhou¹, Long Hu², Zicheng Zhang², Nan Wu³, Jie Sun⁴, Jianzhong Su⁵

Affiliations

¹ School of Ophthalmology & Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China.
² College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
³ Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
⁴ School of Ophthalmology & Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: suncarajie@hotmail.com.
⁵ School of Ophthalmology & Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: sujz@wibe.ac.cn.

Abstract

Patients with colon cancer are often faced a high risk of disease recurrence within 5 years of treatment that is the major cause of cancer mortality. Reliable molecular markers were required to improve the most effective personalized therapy. Here, we identified a recurrence-associated six-lncRNA (long non-coding RNA) signature (LINC0184, AC105243.1, LOC101928168, ILF3-AS1, MIR31HG, and AC006329.1) that can effectively distinguish between high and low risk of cancer recurrence from 389 patients of a discovery dataset, and validated its robust performance in four independent datasets comprising a total of 906 colon cancer patients. We found that the six-lncRNA signature was an independent predictive factor of disease recurrence in multivariate analysis and was superior to the performance of clinical factors and known gene signature. Furthermore, in silico functional analysis showed that the six-lncRNA-signature-associated coding genes are significantly enriched in proliferation and angiogenesis, cell death, as well as critical cancer pathways that could play important roles in colon cancer recurrence. Together, the six-lncRNA signature holds great potential for recurrence risk assessment and personalized management of colon cancer patients.

Keywords: colon cancer; long non-coding RNAs; recurrence; signature.