免疫相关基因特征预测早期结直肠癌患者预后。

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

机构信息

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.

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.

出版信息

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

DOI:10.1016/j.ejso.2020.08.008

PMID:32863096

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.

摘要

目的

免疫相关基因与结直肠癌（CRC）患者的预后相关。本研究旨在评估免疫相关基因特征（IRGS）在预测早期 CRC 患者预后中的作用。

方法

本研究使用 CIT/GSE39582 微阵列数据集，共纳入 309 例 CRC 患者来识别预后相关的 IRGS。将 5 个独立数据集（共包括 1587 例 CRC 患者）分为训练队列（n=566）和两个验证队列（验证-1：n=624；meta-验证：n=397）。对预后进行分析以测试 IRGS 的预测价值。

结果

构建了一个包含 23 个免疫相关基因的预后 IRGS，在训练队列中，该基因可以根据早期疾病（I 期或 II 期）患者的无病生存期将患者分为免疫低风险与高风险组。同样，在验证-1 和 meta-验证队列中，较高的 IRGS 与早期患者的预后显著相关。与 Oncotype DX colon 相比，IRGS 在训练队列中表现出更好的生存相关性。将 IRGS 与临床特征相结合后，IRGS 在多变量分析中仍然是一个独立的预后因素。此外，IRGS 分层的免疫低风险组患者在验证-1 队列中从辅助化疗中获益较少。在鉴定出的免疫高风险组中，有几个生物学过程（包括炎症反应）被富集。与这一发现一致，IRGS 鉴定的免疫高风险组表现出显著增加的免疫和基质细胞浸润。