Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma

作者：Xiaoling Zhang, Yuxin Zhou, Jiahe Hu, Xuefeng Yu, Haitao Xu, Zhichang Ba, Haoxin Zhang, Yanan Sun, Rongfang Wang, Xinlian Du, Ruishu Mou, Xuedong Li, Jiuxin Zhu, Rui Xie · 发表于：BMC Cancer · 年份：2023 · DOI：10.1186/s12885-023-11042-7 · 被引用次数：13 · 研究领域：Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers、Cancer, Hypoxia, and Metabolism

BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. METHODS: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. RESULTS: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT express...