61 metabolites associated with NSCLC.

On a global scale, lung cancer(LC) is the most commonly occurring form of cancer. Nonetheless, the process of screening and detecting it in its early stages presents significant challenges. Earlier research endeavors have recognized metabolites as potentially reliable biomarkers for LC. However, the majority of these studies have been limited in scope, featuring inconsistencies in terms of the relationships and levels of association observed.Moreover, there has been a lack of consistency in the types of biological samples utilized in previous studies. Therefore, the main objective of our research was to explore the correlation between metabolites and Non-small cell lung cancer (NSCLC).Thorough two-sample Mendelian randomization (TSMR) analysis, we investigated potential cause-and-effect relationships between 1400 metabolites and the risk of NSCLC.The analysis of TSMR revealed a significant causal impact of 61 metabolites on NSCLC.To ensure the reliability and validity of our findings, we perform FDR correction for P-values by Benjaminiand Hochberg(BH) method, Our results indicate that Oleate/vaccenate (18:1) levels and Caffeine to paraxanthine ratio may be causally associated with an increased risk of NSCLC [Oleate/vaccenate(18:1)levels: OR = 1.171,95%CI: 1.085–1.265, FDR = 0.036; Caffeine to paraxanthine ratio: OR = 1.386, 95%CI:1.191–1.612,FDR = 0.032].从全球范围来看，肺癌（Lung Cancer, LC）是最为高发的癌症类型。然而，其早期筛查与检测仍面临诸多严峻挑战。既往研究已证实代谢物可作为肺癌潜在的可靠生物标志物，但此类研究大多存在研究范围受限的问题，且所观测到的关联关系与关联强度均存在不一致性。此外，既往研究中所采用的生物样本类型也缺乏统一性。因此，本研究的核心目标为探究代谢物与非小细胞肺癌（Non-small Cell Lung Cancer, NSCLC）之间的关联关系。本研究通过双样本孟德尔随机化（Two-sample Mendelian Randomization, TSMR）分析，探究了1400种代谢物与非小细胞肺癌发病风险之间的潜在因果关联。双样本孟德尔随机化分析结果显示，共有61种代谢物对非小细胞肺癌存在显著的因果影响。为确保研究结果的可靠性与有效性，本研究采用Benjamini-Hochberg（BH）法对P值进行了错误发现率（False Discovery Rate, FDR）校正。研究结果表明，Oleate/vaccenate (18:1)水平以及咖啡因至副黄嘌呤的比值，可能与非小细胞肺癌的发病风险升高存在因果关联[Oleate/vaccenate (18:1)水平：优势比（Odds Ratio, OR）=1.171，95%置信区间（Confidence Interval, CI）=1.085–1.265，FDR=0.036；咖啡因至副黄嘌呤比值：OR=1.386，95%CI=1.191–1.612，FDR=0.032]。