A metabolomics and lipidomics atlas of pulmonary large cell neuroendocrine carcinoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F26%3A10001469" target="_blank" >RIV/00064190:_____/26:10001469 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.biopha.2026.119327" target="_blank" >https://doi.org/10.1016/j.biopha.2026.119327</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopha.2026.119327" target="_blank" >10.1016/j.biopha.2026.119327</a>

Result language

angličtina

Original language name

A metabolomics and lipidomics atlas of pulmonary large cell neuroendocrine carcinoma

Original language description

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive lung cancer with limited therapeutic options and poorly defined metabolic features. To establish a comprehensive molecular overview, we generated the first metabolomics and lipidomics atlas of LCNEC using paired tumor and adjacent non-tumor lung tissues from 34 patients. Untargeted multiplatform liquid chromatography-mass spectrometry profiled 1052 metabolites, revealing extensive remodeling of amino acid, nucleotide, and lipid metabolism. Tumor tissues showed pronounced accumulation of both D- and L-2-hydroxyglutaric acid, indicating altered α-ketoglutarate metabolism independent of IDH1/2 mutations. Newly identified N-lactoyl-amino acids, formed via CNDP2-mediated condensation of lactate and amino acids, were uniformly elevated, suggesting enhanced lactoyl conjugation under elevated lactate levels. Lipidomic profiling revealed widespread reprogramming, including increased phosphatidylcholines, ether-linked phospholipids, polyunsaturated bis(monoacylglycero)phosphates, long-chain triacylglycerols, cholesteryl esters, and acylcarnitines, indicative of lysosomal remodeling and altered mitochondrial fatty acid transport. In addition, the nicotine metabolite cotinine was quantified as an objective biomarker of smoking exposure, revealing discrepancies between measured cotinine levels and self-reported smoking status in several patients. This highlights the value of metabolomics for independently verifying clinical information. Collectively, these data define a hybrid metabolic phenotype bridging features of small and non-small cell lung cancer while revealing unique metabolic signatures of LCNEC. The resulting atlas provides a foundational resource for biomarker discovery and the development of metabolism-based therapeutic strategies in this understudied lung cancer subtype. (C) 2026 The Authors.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

—

OECD FORD branch

30203 - Respiratory systems

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2026

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biomedicine and Pharmacotherapy

ISSN

0753-3322

e-ISSN

—

Volume of the periodical

198

Issue of the periodical within the volume

Neuveden

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

nestránkováno

UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-105034970766