这项全面的研究利用孟德尔随机化的稳健框架，深入研究了心血管相关血浆蛋白与结直肠癌易感性之间存在的复杂因果关系，并采用表达谱和生存分析来揭示相关基因表达中嵌入的潜在临床价值。采用 85 个心血管蛋白的蛋白数量性状位点 (pQTL) 作为工具变量，使用孟德尔随机化方法研究蛋白与 CRC 风险之间的因果关系。根据统计检查，因果推论被分为强、中或弱。药物靶标 MR 检查 VEGF 受体作为结直肠癌治疗靶点的潜力。使用来自癌症基因组图谱 (TCGA) 结直肠癌队列的 RNA-seq 数据对已识别的蛋白质进行差异表达分析、诊断 ROC 曲线和生存分析。使用 cis-pQTL，LOX-1、VEGF-A 和 OPG 与CRC 风险增加（强有力的证据），而 PTX3、TNF-R2 和 MMP-7 具有保护作用（强有力的证据）。 Pan-pQTL 分析发现 MMP-10 增加风险（中等证据），ADM 增加风险（弱证据）。药物靶点MR发现VEGF R1可能是有希望的治疗靶点。差异表达分析显示，编码已识别蛋白质的七个基因在肿瘤中失调。 ROC分析显示5个基因表达具有较高的诊断准确性。 KM 分析显示四个基因具有预后价值。这项大规模 MR 研究表明几种心血管蛋白与 CRC 易感性和进展有关。研究结果强调了 VEGF 信号传导和细胞外基质调节的作用。结果提名特定蛋白质作为潜在的诊断生物标志物或值得进一步研究的治疗靶点。© 2024。作者。

This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions.Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort.Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value.This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.© 2024. The Author(s).