Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target
Zhi-Qing Zhan,
Ze-Min Huang,
Qi-Wen Lan,
Yu-Hua Luo,
Jia-Xin Li,
Ya-Fang Zheng,
Ying-Zhou Chen,
Pei-Zhen Chen,
Tian-Ye Luo,
Baoqing Sun,
Zhangkai J Cheng
Affiliations
Zhi-Qing Zhan
Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Ze-Min Huang
Department of Clinical Medicine, Guangzhou Medical University
Qi-Wen Lan
Department of Clinical Medicine, Guangzhou Medical University
Yu-Hua Luo
Department of Clinical Medicine, Guangzhou Medical University
Jia-Xin Li
Department of Gastroenterology, West China Hospital, Sichuan University
Ya-Fang Zheng
Department of Clinical Medicine, Guangzhou Medical University
Ying-Zhou Chen
Department of Gastroenterology, West China Hospital, Sichuan University
Pei-Zhen Chen
Department of Clinical Medicine, Guangzhou Medical University
Tian-Ye Luo
Department of Clinical Medicine, Guangzhou Medical University
Baoqing Sun
Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Zhangkai J Cheng
Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Abstract Background Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). Methods Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. Results MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01–1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. Conclusion RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.
