Yu Mengjie, Wen Wei, Wang Yue, Shan Xia, Yi Xin, Zhu Wei, Aa Jiye, Wang Guangji
Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Front Oncol. 2024 Mar 19;14:1277206. doi: 10.3389/fonc.2024.1277206. eCollection 2024.
Metabolic reprogramming plays a significant role in the advancement of lung adenocarcinoma (LUAD), yet the precise metabolic changes remain incompletely understood. This study aims to uncover metabolic indicators associated with the progression of LUAD.
A total of 1083 subjects were recruited, including 670 LUAD, 135 benign lung nodules (BLN) and 278 healthy controls (HC). Gas chromatography-mass spectrometry (GC/MS) was used to identify and quantify plasma metabolites. Odds ratios (ORs) were calculated to determine LUAD risk factors, and machine learning algorithms were utilized to differentiate LUAD from BLN.
High levels of oxalate, glycolate, glycine, glyceric acid, aminomalonic acid, and creatinine were identified as risk factors for LUAD (adjusted ORs>1.2, P<0.03). Remarkably, oxalate emerged as a distinctive metabolic risk factor exhibiting a strong correlation with the progression of LUAD (adjusted OR=5.107, P<0.001; advanced-stage vs. early-stage). The Random Forest (RF) model demonstrated a high degree of efficacy in distinguishing between LUAD and BLN (accuracy = 1.00 and 0.73, F1-score= 1.00 and 0.79, and AUC = 1.00 and 0.76 in the training and validation sets, respectively). TCGA and GTEx gene expression data have shown that lactate dehydrogenase A (LDHA), a crucial enzyme involved in oxalate metabolism, is increasingly expressed in the progression of LUAD. High LDHA expression levels in LUAD patients are also linked to poor prognoses (HR=1.66, 95% CI=1.34-2.07, P<0.001).
This study reveals risk factors associated with LUAD.
代谢重编程在肺腺癌（LUAD）进展中起重要作用，但确切的代谢变化仍未完全明确。本研究旨在揭示与LUAD进展相关的代谢指标。
共招募1083名受试者，包括670例LUAD、135例良性肺结节（BLN）和278例健康对照（HC）。采用气相色谱 - 质谱联用（GC/MS）技术鉴定和定量血浆代谢物。计算比值比（OR）以确定LUAD危险因素，并利用机器学习算法区分LUAD与BLN。
草酸盐、乙醇酸盐、甘氨酸、甘油酸、氨基丙二酸和肌酐水平升高被确定为LUAD的危险因素（校正OR>1.2，P<0.03）。值得注意的是，草酸盐成为一种独特的代谢危险因素，与LUAD进展密切相关（校正OR = 5.107，P<0.001；晚期与早期相比）。随机森林（RF）模型在区分LUAD和BLN方面显示出高度有效性（训练集和验证集中的准确率分别为1.00和0.73，F1分数分别为1.00和0.79，AUC分别为1.00和0.76）。TCGA和GTEx基因表达数据表明，乳酸脱氢酶A（LDHA）是草酸盐代谢中的关键酶,在LUAD进展中表达增加。LUAD患者中高LDHA表达水平也与不良预后相关（HR = 1.66，95%CI = 1.34 - 2.07，P<0.001）。
本研究揭示了与LUAD相关的危险因素。
