Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients

Xianwei Mo; Xiaoliang Huang; Yan Feng; Chunyin Wei; Haizhou Liu; Haiming Ru; Haiquan Qin; Hao Lai; Guo Wu; Weishun Xie; Franco Jeen; Yuan Lin; Jungang Liu; Weizhong Tang

doi:10.1080/2162402X.2020.1832347

Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients

Oncoimmunology. 2020 Oct 19;9(1):1832347. doi: 10.1080/2162402X.2020.1832347.

Authors

Xianwei Mo^{1

2}, Xiaoliang Huang^{1

2}, Yan Feng³, Chunyin Wei^{1

2}, Haizhou Liu³, Haiming Ru^{1

2}, Haiquan Qin^{1

2}, Hao Lai^{1

2}, Guo Wu^{1

2}, Weishun Xie^{1

2}, Franco Jeen^{1

2}, Yuan Lin^{1

2}, Jungang Liu^{1

2}, Weizhong Tang^{1

2}

Affiliations

¹ Division of Colorectal & Anal Surgery,Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, the People's Republic of China.
² Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, the People's Republic of China.
³ Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, the People's Republic of China.

Abstract

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy.

Keywords: Colorectal cancer; fluoropyrimidine; immune-related-gene; tumor-infiltrating immune cells.

Publication types

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

MeSH terms

Colorectal Neoplasms* / drug therapy
Humans
Macrophages
Prognosis
Transcriptome*

Grants and funding

This study was funded by the Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project (S2017098); 2019 Guangxi University High-level Innovation Team and the Project of Outstanding Scholars Program, and Guangxi Science and Technology Project (2019AC03004); Guangxi Clinical Research Center for Colorectal Cancer (Guike: AD19245197); Guangxi Science and Technology Project (2019AC03004); National Natural Science Foundation of China [81973533]; Guangxi Science and Technology Research Project (Guike AB18221086).