Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Hunan, China.
School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Hunan, China.
Medicine (Baltimore). 2024 Nov 29;103(48):e40691. doi: 10.1097/MD.0000000000040691.
Understanding the role of the tumor microenvironment in colorectal cancer (CRC) progression remains a challenge due to its complexity. Investigating the interplay between immune cell characteristics, serum metabolites, inflammatory protein factors, and CRC could unveil novel therapeutic avenues. We used 2-sample Mendelian randomization (MR) on Genome-Wide Association Studies (GWAS) data to explore causal links between 731 immune cell characteristics, 1400 serum metabolites, 91 inflammatory proteins, and CRC. Various MR methods, including inverse variance weighted (IVW) and MR-Egger, were applied to ensure robust analysis. Sensitivity analyses, such as the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis, were performed to check for pleiotropy, heterogeneity, and influential outliers. Following rigorous genetic variation screening, we identified 43 immune cell characteristics associated with CRC. Notably, 7 immunophenotypes, including CD39+ CD4+ T cell Absolute Count, exhibited significant associations as protective factors. Additionally, 36 other immunophenotypes showed significant causal relationships with CRC. Among serum metabolites, 37 were correlated with CRC, with 1-arachidonoyl-gpc (20: 4n6) being the most closely linked as a risk factor. Similarly, 36 serum metabolites displayed significant causal relationships with CRC. Seven inflammatory protein factors exhibited causal relationships with CRC, with 4 posing as risk factors and 3 as protective factors. Our study scrutinized 731 immune cell characteristics, 1400 serum metabolites, and 91 inflammatory protein factors within the tumor microenvironment. We confirmed causal relationships between 43 immune cell characteristics, 37 serum metabolites, and 7 inflammatory protein factors with CRC. These findings offer novel insights into the potential etiology, prevention, and treatment strategies for CRC.
了解肿瘤微环境在结直肠癌（CRC）进展中的作用仍然具有挑战性，因为它非常复杂。研究免疫细胞特征、血清代谢物、炎症蛋白因子与 CRC 之间的相互作用，可能会揭示新的治疗途径。我们使用两样本 Mendelian randomization（MR）对基因组关联研究（GWAS）数据进行分析，以探索 731 种免疫细胞特征、1400 种血清代谢物、91 种炎症蛋白因子与 CRC 之间的因果关系。我们应用了各种 MR 方法，包括逆方差加权（Inverse variance weighted，IVW）和 MR-Egger，以确保分析的稳健性。我们还进行了敏感性分析，如 MR-Egger 截距检验、Cochran's Q 检验和逐一剔除分析，以检查是否存在多效性、异质性和有影响力的异常值。经过严格的遗传变异筛选，我们确定了 43 种与 CRC 相关的免疫细胞特征。值得注意的是，7 种免疫表型，包括 CD39+CD4+T 细胞绝对计数，作为保护因素表现出显著的相关性。此外，36 种其他免疫表型与 CRC 也存在显著的因果关系。在血清代谢物中，有 37 种与 CRC 相关，其中 1-花生四烯酰基甘油磷酸胆碱（20:4n6）作为风险因素与 CRC 的相关性最强。同样，有 36 种血清代谢物与 CRC 也存在显著的因果关系。有 7 种炎症蛋白因子与 CRC 存在因果关系，其中 4 种是风险因素，3 种是保护因素。我们的研究深入探讨了肿瘤微环境中的 731 种免疫细胞特征、1400 种血清代谢物和 91 种炎症蛋白因子。我们证实了 43 种免疫细胞特征、37 种血清代谢物和 7 种炎症蛋白因子与 CRC 之间存在因果关系。这些发现为 CRC 的潜在病因学、预防和治疗策略提供了新的见解。
