[结直肠癌炎症蛋白标记物的遗传驱动因素:孟德尔随机方法临床预后研究]。

Q3 Medicine
H Li, G Li, X Zhang, Y Wang
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引用次数: 0

摘要

目的:采用孟德尔随机方法探讨炎症蛋白标记物与结直肠癌风险之间的因果关系:采用孟德尔随机化(MR)方法探讨炎症蛋白标记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 种炎症蛋白标记物作为暴露变量。采用双样本 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 个 MR 模型进行异质性、多效性和敏感性分析,对结果的稳健性进行了评估:反方差加权(IVW)、加权中位数、MR Egger、简单模式和加权模式。我们采用RT-qPCR技术检测了2021年12月至2023年12月期间南方医院收治的86例未经治疗的结直肠腺癌患者的PD-L1、AXIN1和β-NGF的mRNA表达,并分析了它们与患者临床特征的相关性:利用IVW模型,MR分析显示结直肠癌风险降低与AXIN1表达量降低之间存在显著因果关系(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;使用加权中位数模型,OR=0.884,95% CI:0.784-0.998,P=0.047)和PD-L1(OR=0.903,95% CI:0.824- 0.989,P=0.028)。没有观察到明显的异质性或多重性,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分期有明显相关性,尤其是在Ⅳ期患者中(P=0.007)。AXIN1和β-NGF的表达水平与肿瘤的分化程度显著相关,在分化较差的样本中,它们的表达更高(PConclusion:炎症蛋白标记物 AXIN1、β-NGF 和 PD-L1 的低表达与结直肠癌风险的降低存在因果关系,其表达水平与 TNM 分期和肿瘤分化程度相关。因此,这些标记物可作为结直肠癌治疗和预防的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Genetic drivers for inflammatory protein markers in colorectal cancer: a Mendelian randomization approach to clinical prognosis study].

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.

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