Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China.
Metabolomics. 2021 Nov 3;17(11):98. doi: 10.1007/s11306-021-01849-5.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear.
Totally, 128 plasma samples of NSCLC patients were collected before initial treatments, followed by determination of LC-ESI-Q TRAP-MS/MS. Differentially expressed metabolites were screened based on a strict standard.
Based on the integrated platform of targeted metabolome and lipidome, a total of 1141 endogenous metabolites (including 809 lipids) were finally detected in the plasma of NSCLC patients, including 16 increased and 3 decreased endogenous compounds in LUAD group when compared with LUSC group. Thereafter, a logistic regression model integrating four differential metabolites [2-(Methylthio) ethanol, Cortisol, D-Glyceric Acid, and N-Acetylhistamine] was established and could accurately differentiate LUAD and LUSC with an area under the ROC curve of 0.946 (95% CI 0.886-1.000). The cut-off value showed a satisfactory efficacy with 92.0% sensitivity and 92.9% specificity. KEGG functional enrichment analysis showed these differentially expressed metabolites could be further enriched in riboflavin metabolism, steroid hormone biosynthesis, prostate cancer, etc. The endogenous metabolites identified in this study have the potential to be used as novel biomarkers to distinguish LUAD from LUSC.
Our research might provide more evidence for exploring the pathogenesis and differentiation of NSCLC. This research could promote a deeper understanding and precise treatment of lung cancer.
非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。肺腺癌（LUAD）和鳞状细胞癌（LUSC）是 NSCLC 最常见的亚型。尽管 LUAD 和 LUSC 之间的遗传差异已经得到深入阐明，但这两种亚型的代谢差异仍不清楚。
总共收集了 128 例 NSCLC 患者在初始治疗前的血浆样本，随后通过 LC-ESI-Q TRAP-MS/MS 进行测定。基于严格的标准筛选差异表达的代谢物。
基于靶向代谢组学和脂质组学的综合平台，最终在 NSCLC 患者的血浆中检测到 1141 种内源性代谢物（包括 809 种脂质），与 LUSC 组相比，LUAD 组有 16 种内源性化合物增加，3 种内源性化合物减少。此后，建立了一个整合了四个差异代谢物[2-（甲基硫代）乙醇、皮质醇、D-甘油酸和 N-乙酰组氨酸]的逻辑回归模型，能够准确地区分 LUAD 和 LUSC，ROC 曲线下面积为 0.946（95%CI 0.886-1.000）。该截断值具有良好的疗效，敏感性为 92.0%，特异性为 92.9%。KEGG 功能富集分析表明，这些差异表达的代谢物可进一步富集于核黄素代谢、类固醇激素生物合成、前列腺癌等途径。本研究中鉴定的内源性代谢物有可能成为区分 LUAD 和 LUSC 的新型生物标志物。
我们的研究可能为探索 NSCLC 的发病机制和分化提供更多证据。本研究可以促进对肺癌的深入理解和精准治疗。
