Dissecting the prognostic role of metabolic markers in lung neuroendocrine Tumors: The MONET study

作者：Giulia Pasello, Giulia Pigato, C. Mulargiu, Federica Ferrarini, Federica Pezzuto, Marco Schiavon, Alessandra Ferro, Daniela Scattolin, Alessandro Dal Maso, S. Frega, Laura Bonanno, Fiorella Calabrese, Andrea Dell’Amore, Valentina Guarneri, Stefano Indraccolo · 发表于：Lung Cancer · 年份：2026 · DOI：10.1016/j.lungcan.2026.109404 · 被引用次数：1 · 研究领域：Neuroendocrine Tumor Research Advances、Lung Cancer Research Studies、Cancer, Hypoxia, and Metabolism

BACKGROUND: Lung neuroendocrine tumors (LNETs) span well-differentiated typical/atypical carcinoids (TC/AC) to poorly differentiated large-cell neuroendocrine carcinoma (LCNEC). Robust biomarkers for grading and prognostication are lacking. We hypothesized that differential metabolic pathways activation, reflected by protein expression, holds prognostic relevance. We conducted a monocentric translational study on resected LNETs to characterize biomarkers involved in glycolysis, fatty acid, and amino acid pathways across different grades of LNETs. Secondary endpoints included assessing clinical outcomes and correlating biomarker expression with patient prognosis. METHODS: Digital FFPE sections underwent standardized immunohistochemistry (IHC) and quantitative image analysis. Biomarkers included glycolysis (MCT1, MCT4, CD147), amino-acid metabolism (SLC1A5, SLC7A5, GLS), and fatty-acid synthesis (FAS, ACC). Expression was summarized by H-score and dichotomized. Associations with clinicopathologic variables, recurrence-free survival (RFS), and overall survival (OS) were tested using median and maximally selected rank statistics. RESULTS: Overall, 49 LNETs were included: 11 TC, 19 AC; 19 LCNEC. LCNEC showed marked upregulation of glycolytic and amino-acid transport markers versus TC/AC. Fatty-acid markers were generally low across subtypes. High MCT1 and SLC7A5 predicted shorter OS; MCT1 and CD147 predicted shorter RFS. In multivariable analysis, MCT1 remained independently assoc...