Li H, Li G, Zhang X, Wang Y
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 511340, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Jul 20;44(7):1361-1369. doi: 10.12122/j.issn.1673-4254.2024.07.16.
To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization (MR) approach.
We obtained data pertaining to colorectal cancer from Genome-Wide Association Study (GWAS) datasets and used 91 inflammatory protein markers as the exposure variables. A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk. The robustness of the results was evaluated through heterogeneity, pleiotropy, and sensitivity analyses using 5 MR models: Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Simple Mode, and Weighted Mode. We examined the mRNA expressions of -, , and - using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December, 2021 and December 2023, and analyzed their correlation with the clinical characteristics of the patients.
Using the IVW model, MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1 (OR=0.866, 95% : 0.754-0.994, =0.040), β-NGF (OR=0.914, 95% : 0.843-0.990, =0.028; OR=0.884, 95% : 0.784-0.998, =0.047 using Weighted Median model), and PD-L1 (OR=0.903, 95% : 0.824- 0.989, =0.028). No significant heterogeneity or pleiotropy was observed, indicating good stability of the results. Sensitivity analysis confirmed the reliability of the findings. The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging, particularly in stage Ⅳ patients (=0.007). AXIN1 and β -NGF expression levels were significantly correlated with the degree of tumor differentiation, and their expressions were higher in poorly differentiated samples (<0.001).
Lowered expressions of inflammatory protein markers AXIN1, β-NGF, and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation. These markers may thus serve as potential targets for colorectal cancer treatment and prevention.
采用孟德尔随机化（MR）方法探讨炎症蛋白标志物与结直肠癌风险之间的因果关系。
我们从全基因组关联研究（GWAS）数据集中获取了结直肠癌相关数据，并使用91种炎症蛋白标志物作为暴露变量。采用两样本MR分析模型评估炎症标志物与结直肠癌风险之间的因果联系。通过使用5种MR模型（逆方差加权法（IVW）、加权中位数法、MR-Egger法、简单模式法和加权模式法）进行异质性、多效性和敏感性分析来评估结果的稳健性。我们使用RT-qPCR检测了2021年12月至2023年12月期间在南方医院收治的86例未经治疗的结直肠腺癌患者中-、-和-的mRNA表达，并分析了它们与患者临床特征的相关性。
使用IVW模型，MR分析显示结直肠癌风险降低与AXIN1表达降低（OR=0.866，95%可信区间：0.754-0.994，P=0.040）、β-NGF表达降低（OR=0.914，95%可信区间：0.843-0.990，P=0.028；使用加权中位数模型时OR=0.884，95%可信区间：0.784-0.998，P=0.047）以及PD-L1表达降低（OR=0.903，95%可信区间：0.824-0.989，P=0.028）之间存在显著的因果关联。未观察到显著的异质性或多效性，表明结果具有良好的稳定性。敏感性分析证实了研究结果的可靠性。临床研究表明PD-L1表达与TNM分期之间存在显著相关性，尤其是在Ⅳ期患者中（P=0.007）。AXIN1和β-NGF表达水平与肿瘤分化程度显著相关，且在低分化样本中表达较高（P<0.001）。
炎症蛋白标志物AXIN1、β-NGF和PD-L1表达降低与结直肠癌风险降低存在因果关联，且它们的表达水平与TNM分期和肿瘤分化相关。因此，这些标志物可能作为结直肠癌治疗和预防的潜在靶点。
