南方医科大学学报2024，Vol.44Issue(7)：1361-1369,9.DOI:10.12122/j.issn.1673-4254.2024.07.16
直肠癌炎症蛋白因子的遗传驱动:孟德尔随机化方法在临床预后研究中的应用
Genetic drivers for inflammatory protein markers in colorectal cancer:a Mendelian randomization approach to clinical prognosis study
摘要
Abstract
Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods 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 PD-L1,AXIN1,and β-NGF 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.Results 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%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=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(P=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(P<0.001).Conclusion 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.关键词
直肠癌/炎症蛋白因子/孟德尔随机化/临床研究Key words
colorectal cancer/inflammatory protein markers/Mendelian randomization/clinical study引用本文复制引用
李和平,李高桦,张学华,王亚楠..直肠癌炎症蛋白因子的遗传驱动:孟德尔随机化方法在临床预后研究中的应用[J].南方医科大学学报,2024,44(7):1361-1369,9.基金项目
广东省胃肠道肿瘤精准医学重点实验室(2020B121201004) （2020B121201004）
广东省重大人才项目(2019JC05Y361) （2019JC05Y361）
广东省区域联合基金(2020A1515110140) （2020A1515110140）
广州市科技计划项目(202206011130280011) （202206011130280011）
