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.
Yan Li  1 ,  Bing Wang  1 ,  Fahan Ma  1 ,  Dongxian Jiang  2 ,  Ying Wang  1 ,  Kai Li  1 ,  Subei Tan  1 ,  Jinwen Feng  1 ,  Yunzhi Wang  1 ,  Zhaoyu Qin  1 ,  Ganfei Xu  1 ,  Sha Tian  1 ,  Xiaolei Zhang  2 ,  Chen Xu  3 ,  Jiaxue Wu  4 ,  Jianmin Xu  5 ,  Yingyong Hou  6 ,  Chen Ding  7
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].
PMID: 38086380 DOI: 10.1016/j.xcrm.2023.101311
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.