肝脏肿瘤发生伴随着血液中明显的蛋白质变化。通过采用血浆蛋白质组分析，我们可以深入研究肝癌的分子机制并查明潜在的生物标志物。在这项巢式病例对照研究中，我们应用液相色谱-串联质谱法对基线血浆样本中的蛋白质组进行分析。确定差异蛋白表达并进行功能富集、网络和孟德尔随机化 (MR) 分析。我们鉴定出 193 种蛋白质，各组之间水平存在显着差异。在这些蛋白质中，MR 分析表明载脂蛋白 B (APOB) 与肝癌之间存在令人信服的负相关关系。这种关联在英国生物银行队列中得到了进一步证实：基因预测的 APOB 水平与肝癌风险降低 31% (95% CI 19-42%) 相关；表型分析表明，循环 APOB 水平每增加 0.1 g/L，肝癌风险就会降低 11% (95% CI 8-14%)。多变量 MR 分析表明，肝脏脂肪含量可能完全介导 APOB 与肝癌的关系。总之，我们确定了一些血浆蛋白，特别是 APOB，作为肝癌的潜在生物标志物。我们的研究结果强调了脂质代谢与肝癌之间的复杂联系，为有针对性的预防策略和早期检测提供了线索。

Liver oncogenesis is accompanied by discernible protein changes in the bloodstream. By employing plasma proteomic profiling, we can delve into the molecular mechanisms of liver cancer and pinpoint potential biomarkers. In this nested case-control study, we applied liquid chromatography-tandem mass spectrometry for proteome profiling in baseline plasma samples. Differential protein expression was determined and was subjected to functional enrichment, network, and Mendelian randomization (MR) analyses. We identified 193 proteins with notable differential levels between the groups. Of these proteins, MR analysis offered a compelling negative association between apolipoprotein B (APOB) and liver cancer. This association was further corroborated in the UK Biobank cohort: genetically predicted APOB levels were associated with a 31% (95% CI 19-42%) decreased risk of liver cancer; and phenotypic analysis indicated an 11% (95% CI 8-14%) decreased liver cancer risk for every 0.1 g/L increase of circulating APOB levels. Multivariable MR analysis suggested that the hepatic fat content might fully mediate the APOB-liver cancer connection. In summary, we identified some plasma proteins, particularly APOB, as potential biomarkers of liver cancer. Our findings underscore the intricate link between lipid metabolism and liver cancer, offering hints for targeted prophylactic strategies and early detection.