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Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model.

ABSTRACT: 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.

SUBMITTER: Sun T

PROVIDER: S-EPMC11018865 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model.

Sun Ting T Chen Junge J Yang Fan F Zhang Gang G Chen Jiahao J Wang Xun X Zhang Jing J

EMBO molecular medicine 20240311 4

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 fur ...[more]

PMID: 38467839

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Project description:Background: Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods: we integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results: Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions: Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.

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Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model.

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Lipidomics reveals new lipid-based lung adenocarcinoma early diagnosis model.

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