Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model

• Published in: EMBO molecular medicine 2024-04, Vol.16 (4), p.854-869
• Main Authors: Sun, Ting, Chen, Junge, Yang, Fan, Zhang, Gang, Chen, Jiahao, Wang, Xun, Zhang, Jing
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Early Diagnosis Model; EMBO02; EMBO03; EMBO35; Lipid Metabolism; Lipidomics; LSRscore; LUAD; Molecular Medicine
• ISSN: 1757-4684; 1757-4676; 1757-4684
• DOI: 10.1038/s44321-024-00052-y

Lung adenocarcinoma (LUAD) continues to pose a significant mortality risk with a lack of dependable biomarkers for early noninvasive cancer detection. Here, we find that aberrant lipid metabolism is significantly enriched in lung cancer cells. Further, we identified four signature lipids highly associated with LUAD and developed a lipid signature-based scoring model (LSRscore). Evaluation of LSRscore in a discovery cohort reveals a robust predictive capability for LUAD (AUC: 0.972), a result further validated in an independent cohort (AUC: 0.92). We highlight one lipid signature biomarker, PE(18:0/18:1), consistently exhibiting altered levels both in cancer tissue and in plasma of LUAD patients, demonstrating significant predictive power for early-stage LUAD. Transcriptome analysis reveals an association between increased PE(18:0/18:1) levels and dysregulated glycerophospholipid metabolism, which consistently displays strong prognostic value across two LUAD cohorts. The combined utility of LSRscore and PE(18:0/18:1) holds promise for early-stage diagnosis and prognosis of LUAD. Synopsis Early detection of lung cancer by developing reliable biomarkers to improve the prognosis of lung adenocarcinoma (LUAD) patients is urgently needed. In this study we identified four signature lipids highly associated with LUAD and developed a lipid signature-based scoring model (LSRscore) for early cancer diagnosis. LSRscore achieves AUC > 0.9 in a discovery cohort and in an independent validation cohort. Lipid signature biomarker, PE(18:0/18:1), exhibits a strong predictive power for early-stage LUAD. Increased levels of PE(18:0/18:1) are associated with dysregulated glycerophospholipid metabolism. Early detection of lung cancer by developing reliable biomarkers to improve the prognosis of lung adenocarcinoma (LUAD) patients is urgently needed. In this study we identified four signature lipids highly associated with LUAD and developed a lipid signature-based scoring model (LSRscore) for early cancer diagnosis.