Plasma metabolomics reveals risk factors for lung adenocarcinoma

Mengjie Yu; Wei Wen; Yue Wang; Xia Shan; Xin Yi; Wei Zhu; Jiye Aa; Guangji Wang

doi:10.3389/fonc.2024.1277206

Plasma metabolomics reveals risk factors for lung adenocarcinoma

Front Oncol. 2024 Mar 19:14:1277206. doi: 10.3389/fonc.2024.1277206. eCollection 2024.

Authors

Mengjie Yu^#¹, Wei Wen^#², Yue Wang^#¹, Xia Shan³, Xin Yi¹, Wei Zhu⁴, Jiye Aa¹, Guangji Wang¹

Affiliations

¹ Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
² Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
³ Department of Respiration, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: This study reveals risk factors associated with LUAD.

Keywords: LDHA; LUAD; metabolomics; oxalate; risk factor.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was financially supported by the leading technology foundation research project of Jiangsu province (BK20192005); the National Natural Science Foundation of the People’s Republic of China (82173890); the CAMS Innovation Fund for Medical Sciences (CIFMS2021-I2M-5-011); the Fundamental Research Funds for the Central Universities (3012300076); the Postdoctoral Foundation of Jiangsu Province (1412300075).