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, Guangzhou, China.
Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.
BMC Cancer. 2024 Jun 10;24(1):714. doi: 10.1186/s12885-024-12466-5.
Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC).
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.
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.
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.
本研究旨在探讨类风湿关节炎（RA）与结直肠癌（CRC）之间的关系、共享基因特征以及潜在的发病机制。
采用孟德尔随机化（MR）分析评估 RA 与 CRC 之间的因果关系。利用 eQTL 数据进行基于汇总统计数据的孟德尔随机化（SMR）分析，以确定与 CRC 相关的因果基因。综合单细胞 RNA 测序和批量 RNA 测序分析，全面研究 RA 和 CRC 发病机制中的共享基因特征和潜在机制。预测 CRC 免疫治疗反应中共享枢纽基因的作用。进行泛癌分析以探讨 MYO9A 在 33 种人类肿瘤中的潜在作用。
MR 分析表明，RA 可能与 CRC 的发病风险轻度增加相关（优势比=1.04，95%置信区间=1.01-1.07，P=0.005）。结合转录组分析的 SMR 分析确定 MYO9A 是 CRC 的一个因果基因，也是 RA 和 CRC 中的一个共享基因特征。MYO9A 可能有助于肿瘤抑制，而 MYO9A 的下调可能通过破坏上皮极性和结构影响 CRC 肿瘤发生，导致 CRC 预后较差。此外，MYO9A 有望成为 CRC 预后和免疫治疗反应的强大预测生物标志物。泛癌分析表明，MYO9A 可能在多种人类癌症的发生和进展中具有保护作用。
RA 可能与 CRC 的发病风险轻度增加相关。MYO9A 是 CRC 和 RA 的一个共享基因特征和潜在的免疫相关治疗靶点。靶向 MYO9A 介导的极性和上皮结构丧失可能是 CRC 的一种新的治疗方法。
