Autophagy and biotransformation affect sorafenib resistance in hepatocellular carcinoma

Ruiqi Zheng; Shuang Weng; Jianping Xu; Zhuo Li; Yaru Wang; Zulihumaer Aizimuaji; Sheng Ma; Linlin Zheng; Haiyang Li; Wantao Ying; Weiqi Rong; Ting Xiao

doi:10.1016/j.csbj.2023.07.005

Autophagy and biotransformation affect sorafenib resistance in hepatocellular carcinoma

Comput Struct Biotechnol J. 2023 Jul 5:21:3564-3574. doi: 10.1016/j.csbj.2023.07.005. eCollection 2023.

Authors

Ruiqi Zheng¹, Shuang Weng², Jianping Xu³, Zhuo Li⁴, Yaru Wang¹, Zulihumaer Aizimuaji¹, Sheng Ma¹, Linlin Zheng⁵, Haiyang Li⁵, Wantao Ying^{2

6}, Weiqi Rong⁵, Ting Xiao¹

Affiliations

¹ State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China.
³ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing 100021, China.
⁴ Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing 100021, China.
⁵ Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
⁶ College of Life Science and Bioengineering, Beijing University of Technology, No. 100, Pingleyuan, Chaoyang District, Beijing 100124, China.

Abstract

As sorafenib is a first-line drug for treating advanced hepatocellular carcinoma, sorafenib resistance has historically attracted attention. However, most of this attention has been focused on a series of mechanisms related to drug resistance arising after sorafenib treatment. In this study, we used proteomic techniques to explore the potential mechanisms by which pretreatment factors affect sorafenib resistance. The degree of redundant pathway PI3K/AKT activation, biotransformation capacity, and autophagy level in hepatocellular carcinoma patients prior to sorafenib treatment might affect their sensitivity to sorafenib, in which ADH1A and STING1 are key molecules. These three factors could interact mechanistically to promote tumor cell survival, might be malignant features of tumor cells, and are associated with hepatocellular carcinoma prognosis. Our study suggests possible avenues of therapeutic intervention for patients with sorafenib-resistance and the potential application of immunotherapy with the aim of improving the survival of such patients.

Keywords: Autophagy; Biotransformation; HCC; PI3K/AKT/mTOR; Proteomics; Sorafenib resistance.