Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients

Jia Ke; Xuan-Hui Liu; Xiao-Feng Jiang; Zhen He; Jian Xiao; Bin Zheng; Yu-Feng Chen; Ze-Rong Cai; Xiao-Bin Zheng; Yi-Feng Zou; Ping Lan; Xiao-Jian Wu; Feng Gao

doi:10.1016/j.ejso.2020.08.008

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients

Eur J Surg Oncol. 2020 Oct;46(10 Pt B):e62-e70. doi: 10.1016/j.ejso.2020.08.008. Epub 2020 Aug 14.

Authors

Jia Ke¹, Xuan-Hui Liu¹, Xiao-Feng Jiang¹, Zhen He¹, Jian Xiao², Bin Zheng¹, Yu-Feng Chen¹, Ze-Rong Cai¹, Xiao-Bin Zheng¹, Yi-Feng Zou¹, Ping Lan³, Xiao-Jian Wu⁴, Feng Gao⁵

Affiliations

¹ Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, Guangdong, China.
² Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, Guangdong, China; Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
³ Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, Guangdong, China. Electronic address: lanping@mail.sysu.edu.cn.
⁴ Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, Guangdong, China. Electronic address: wuxjian@mail.sysu.edu.cn.
⁵ Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, Guangzhou, Guangdong, China. Electronic address: gaof57@mail.sysu.edu.cn.

PMID: 32863096
DOI: 10.1016/j.ejso.2020.08.008

Abstract

Aim: Immune-related genes are associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of an immune-related gene signature (IRGS) in predicting the prognosis of early-stage CRC patients.

Methods: In total, 309 CRC patients were selected for the identification of prognostic IRGS using the CIT/GSE39582 microarray dataset. Five independent datasets including 1587 CRC patients were divided into a training cohort (n = 566) and two validation cohorts (n = 624 in validation-1 and n = 397 in meta-validation). Prognostic analyses were performed to test the predictive value of IRGS.

Results: A prognostic IRGS that included 23 immune-related genes was constructed and significantly stratified patients into immune low-vs. high-risk groups in terms of disease-free survival using patients with early-stage disease (I or II) in the training cohort. Similarly, a higher IRGS was correlated with significantly worse prognosis of early-stage patients in validation-1 and meta-validation cohorts. Compared with Oncotype DX colon, we found that IRGS exhibited an improved survival correlation in the training cohort. After integration with clinical characteristics, IRGS remained as an independent prognostic factor in multivariate analysis. Furthermore, IRGS-stratified immune low-risk group patients gained less benefit from adjuvant chemotherapy in the validation-1 cohort. Several biological processes, including inflammatory response, were enriched among genes in identified the immune high-risk group. Consistent with this finding, the IRGS-identified immune high-risk group exhibited significantly increased immune and stromal cell infiltration.

Conclusion: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those with early-stage disease.

Keywords: Colorectal cancer; Immune-related gene signature; Prediction; Prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma / genetics*
Carcinoma / immunology
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / immunology
Databases, Genetic
Disease-Free Survival
Humans
Immune System Phenomena / genetics*
Neoplasm Staging
Prognosis
Proportional Hazards Models
Reproducibility of Results
Transcriptome*