Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies reveals potential therapeutic strategies

Yan Li; Bing Wang; Fahan Ma; Dongxian Jiang; Ying Wang; Kai Li; Subei Tan; Jinwen Feng; Yunzhi Wang; Zhaoyu Qin; Ganfei Xu; Sha Tian; Xiaolei Zhang; Chen Xu; Jiaxue Wu; Jianmin Xu; Yingyong Hou; Chen Ding

doi:10.1016/j.xcrm.2023.101311

Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies reveals potential therapeutic strategies

Cell Rep Med. 2023 Dec 19;4(12):101311. doi: 10.1016/j.xcrm.2023.101311. Epub 2023 Dec 11.

Authors

Yan Li¹, Bing Wang¹, Fahan Ma¹, Dongxian Jiang², Ying Wang¹, Kai Li¹, Subei Tan¹, Jinwen Feng¹, Yunzhi Wang¹, Zhaoyu Qin¹, Ganfei Xu¹, Sha Tian¹, Xiaolei Zhang², Chen Xu³, Jiaxue Wu⁴, Jianmin Xu⁵, Yingyong Hou⁶, Chen Ding⁷

Affiliations

¹ State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai 200433, China.
² Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁴ State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai 200433, China. Electronic address: [email protected].
⁵ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁶ Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁷ State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai 200433, China. Electronic address: [email protected].

Abstract

Chemoradiation and targeted therapies are the major treatments for colorectal cancer (CRC); however, molecular properties associated with therapy resistance are incompletely characterized. Here, we profile the proteome of 254 tumor tissues from patients with CRC undergoing chemotherapy, chemoradiation, or chemotherapy combined with targeted therapy. Proteome-based classification reveals four subtypes featured with distinct biological and therapeutic characteristics. The integrative analysis of CRC cell lines and clinical samples indicates that immune regulation is significantly associated with drug sensitivity. HSF1 can increase DNA damage repair and cell cycle, thus inducing resistance to radiation, while high expression of HDAC6 is negatively associated with response of cetuximab. Furthermore, we develop prognostic models with high accuracy to predict the therapeutic response, further validated by parallel reaction monitoring (PRM) assay in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemoradiation and targeted therapy in CRC.

Keywords: chemoradiation and targeted therapies; colorectal cancer; parallel reaction monitoring; prognostic models; proteome-based classification; therapeutic response.

Publication types

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

MeSH terms

Cetuximab / pharmacology
Cetuximab / therapeutic use
Colorectal Neoplasms* / drug therapy
Humans
Prognosis
Proteome
Proteomics

Substances

Proteome
Cetuximab