文章：

胰腺导管腺癌中代谢相关分子模式的特征

Features of metabolism associated molecular patterns in pancreatic ductal adenocarcinoma 

原文发布日期：2023-07-06 

英文摘要：

Exploring pancreatic ductal adenocarcinoma (PDAC) metabolic landscape would contribute to further understand PDAC from the metabolic perspective and provide more details for precise treatment design. This study aims to describe metabolic landscape of PDAC. Bioinformatics analysis was used to investigate the differences of genome, transcriptome, and proteome levels of metabolic patterns. Three subtypes (MC1, MC2, and MC3) were identified and characterized as distinct metabolic patterns. MC1, enriched in lipid metabolism and amino acid metabolism signatures, was associated with lower abundance of immune cells and stromal cells, and non-response to immunotherapy. MC2 displayed immune-activated characteristics, minor genome alterations and good response to immunotherapy. MC3 was characterized by high glucose metabolism, high pathological grade, immune-suppressed features, poor prognosis, and epithelial-mesenchymal transition phenotype. A ninety-three gene classifier preformed robust prediction and high accuracy (training set: 93.7%; validation set 1: 85.0%; validation set 2: 83.9%). Using random forest classifier, probabilities of three patterns could be predicted on pancreatic cancer cell lines, which could be used to find vulnerable targets in response to both genetic and drug perturbation. Our study revealed features of PDAC metabolic landscape, which could be expected to provide a reference for prognosis prediction and precise treatment design. 

摘要翻译： 

探索胰腺导管腺癌（PDAC）的代谢景观有助于从代谢角度进一步理解PDAC，并为精准治疗设计提供更多细节。本研究旨在描述PDAC的代谢特征。通过生物信息学分析研究了代谢模式在基因组、转录组和蛋白质组水平的差异，鉴定出三种具有独特代谢模式的亚型（MC1、MC2和MC3）。MC1富集脂质代谢和氨基酸代谢特征，其免疫细胞与基质细胞浸润程度较低，且对免疫治疗无应答；MC2呈现免疫激活特性、基因组变异较少，对免疫治疗反应良好；MC3则以高葡萄糖代谢、高病理分级、免疫抑制特性、不良预后及上皮-间质转化表型为特征。基于93个基因构建的分类器表现出稳健的预测能力和高精度（训练集：93.7%；验证集1：85.0%；验证集2：83.9%）。通过随机森林分类器可预测胰腺癌细胞系中三种模式的概率，这有助于发现针对遗传和药物扰动的易感靶点。本研究揭示了PDAC代谢景观的特征，有望为预后预测和精准治疗设计提供参考依据。

原文链接：

Features of metabolism associated molecular patterns in pancreatic ductal adenocarcinoma