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

• DOI: 10.1016/j.xcrm.2023.101311
• Publication Date: 2023-12-11T15:38:41Z
• Authors: 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
• Keywords: Proteomics; Proteome; Humans; Cetuximab; Colorectal Neoplasms; Prognosis; Article

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.