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乳腺癌中RON和DEK依赖性信号传导的脂质谱分析有助于发现预测不良预后的基因网络。

Lipid profiling of RON and DEK-dependent signaling in breast cancer guides discovery of gene networks predictive of poor outcomes.

作者信息

Vicente-Muñoz Sara, Davis James C, Lane Adam, Lane Andrew N, Waltz Susan E, Wells Susanne I

机构信息

Translational Metabolomics Facility, Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States.

出版信息

Front Oncol. 2024 Sep 16;14:1382986. doi: 10.3389/fonc.2024.1382986. eCollection 2024.

DOI:10.3389/fonc.2024.1382986
PMID:39351361
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11440356/
Abstract

Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK oncoproteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but their influence on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, a nuclear magnetic resonance (NMR)-based approach was utilized. The observed differences identified a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis-free survival (DMFS), post-progression survival (PPS), and recurrence-free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, whereas DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts poor outcomes for patients with breast cancer patients. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence.

摘要

复发性和转移性乳腺癌通常对治疗具有抗性。大量证据表明，重编程的脂质代谢会促进癌症复发。乳腺癌中RON和DEK癌蛋白的过表达与不良预后相关。这两种蛋白在实验室模型中均会促进癌症转移，但它们对脂质代谢物水平的影响仍不清楚。为了测量RON和DEK依赖性稳态脂质代谢物水平，采用了基于核磁共振（NMR）的方法。观察到的差异确定了一种与脂质代谢相关的基因表达特征，该特征可预测乳腺癌患者的总生存期（OS）、无远处转移生存期（DMFS）、进展后生存期（PPS）和无复发生存期（RFS）。RON缺失导致胆固醇和鞘磷脂水平降低，而DEK缺失则使总脂肪酸水平升高，游离甘油水平降低。然后对与脂质相关的基因进行查询，以确定一种可预测乳腺癌患者不良预后的特征。综上所述，RON和DEK以一种可预测并可能促进乳腺癌转移和复发的方式差异性地调节脂质代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1967/11440356/5d41da86fa81/fonc-14-1382986-g009.jpg
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