Jiang Wei, Zheng You, Fang Huiying
Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Rd, Yuzhong District, Chongqing, 400010, China.
Department of Breast Diseases, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing University Cancer Hospital, No. 181 Hanyu Rd, Shapingba District, Chongqing, 400030, China.
Discov Oncol. 2025 Apr 29;16(1):638. doi: 10.1007/s12672-025-02443-0.
Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Increasing evidence suggests that alterations in the immune system may play a pivotal role in the initiation and progression of CRC. However, the precise causal relationship between specific immune cell phenotypes and CRC remains incompletely understood. Elucidating this connection may unveil novel therapeutic targets for the treatment of CRC.
To explore the causal relationship between immune cell phenotypes and CRC, we conducted a comprehensive bidirectional Mendelian randomization (MR) analysis. Genetic variants were utilized as instrumental variables (IVs), with the inverse variance weighting (IVW) method employed to assess the effect of specific immune cell phenotypes on CRC risk. Sensitivity analysis were performed to evaluate the robustness of our findings, while heterogeneity analysis were conducted to minimize the potential impact of pleiotropy.
Our MR analysis revealed potential causal associations between various immune phenotypes and CRC. Specifically, 34 immune cell types were found to be potentially causally associated with colon cancer, while 29 immune cell types showed a potential causal relationship with rectal cancer. Sensitivity analysis further confirmed the robustness of these associations, suggesting that these immune cell phenotypes may play a significant role in the development of CRC.
Our study provides evidence for a causal relationship between immune cell phenotypes and CRC. These findings suggest that immune cell characteristics may serve as potential biomarkers for CRC and could represent novel therapeutic targets. However, further experimental research is needed to explore the underlying mechanisms in greater detail and to validate the clinical applicability of these findings.
结直肠癌(CRC)仍然是全球癌症相关死亡的主要原因之一。越来越多的证据表明,免疫系统的改变可能在CRC的发生和发展中起关键作用。然而,特定免疫细胞表型与CRC之间的确切因果关系仍未完全了解。阐明这种联系可能会揭示CRC治疗的新靶点。
为了探索免疫细胞表型与CRC之间的因果关系,我们进行了全面的双向孟德尔随机化(MR)分析。将基因变异用作工具变量(IVs),采用逆方差加权(IVW)方法评估特定免疫细胞表型对CRC风险的影响。进行敏感性分析以评估我们研究结果的稳健性,同时进行异质性分析以尽量减少多效性的潜在影响。
我们的MR分析揭示了各种免疫表型与CRC之间的潜在因果关联。具体而言,发现34种免疫细胞类型与结肠癌存在潜在因果关联,而29种免疫细胞类型与直肠癌存在潜在因果关系。敏感性分析进一步证实了这些关联的稳健性,表明这些免疫细胞表型可能在CRC的发展中起重要作用。
我们的研究为免疫细胞表型与CRC之间的因果关系提供了证据。这些发现表明,免疫细胞特征可能作为CRC的潜在生物标志物,并可能代表新的治疗靶点。然而,需要进一步的实验研究来更详细地探索潜在机制,并验证这些发现的临床适用性。