Crosstalk of non-apoptotic RCD panel in hepatocellular carcinoma reveals the prognostic and therapeutic optimization
Shuo Li,
Yaqi Xu,
Xin Hu,
Hao Chen,
Xiaodan Xi,
Fei Long,
Yuan Rong,
Jun Wang,
Chunhui Yuan,
Chen Liang,
Fubing Wang
Affiliations
Shuo Li
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Yaqi Xu
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Xin Hu
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Hao Chen
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Xiaodan Xi
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Fei Long
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Yuan Rong
Forensic Center of Justice, Zhongnan Hospital of Wuhan University, Wuhan China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Jun Wang
Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China; Corresponding author
Chunhui Yuan
Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Corresponding author
Chen Liang
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan 430071, China; Corresponding author
Fubing Wang
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China; Corresponding author
Summary: Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients’ tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.
