Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Institute of Nature Conservation, Polish Academy of Sciences, Krakow, Poland.
Aging (Albany NY). 2023 Oct 18;15(20):11331-11368. doi: 10.18632/aging.205130.
The purpose of the study was to investigate the role of exosome and lipid metabolism-related genes (EALMRGs) mRNA levels in the diagnosis and prognosis of Pancreatic Adenocarcinoma (PAAD).
The mRNA expression pattern of PAAD and pan-cancers with prognostic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. EALMRGs were acquired from GeneCards and MSigDB database after merging and deduplication. Prognostic EALMRGs were screened through univariate COX regression analysis, and a prognostic model was constructed based on these genes by least absolute shrinkage and selection operator (LASSO) regression. The prognostic value of EALMRGs was then validated in pan-cancer data. The time characteristics ROC curve analysis was performed to evaluate the effectiveness of the prognostic genes.
We identified 5 hub genes (ABCB1, CAP1, EGFR, PPARG, SNCA) according to high and low-risk groups of prognoses. The risk formula was verified in three other cohort of pancreatic cancer patients and was explored in pan-cancer data. Additionally, T cell and dendritic cell infiltration was significantly increased in low-risk group. The expression of the 5 hub genes was also identified in single-cell sequencing data of pancreatic cancer with pivotal pathways. Additionally, functional enrichment analysis based on pancreatic cancer data in pancreatic cancer showed that protein serine/threonine kinase activity, focal adhesion, actin binding, cell-substrate junction, organic acid transport, and regulation of transporter activity were significant related to the expression of genes in EALMRGs.
Our risk formula shows potential prognostic value in multiple cancers and manifest pivotal alterations in immune infiltration and biological pathway in pancreatic cancer.
本研究旨在探讨外泌体和脂质代谢相关基因（EALMRGs）mRNA 水平在胰腺导管腺癌（PAAD）诊断和预后中的作用。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据库中获取 PAAD 和具有预后数据的泛癌mRNA 表达谱。从 GeneCards 和 MSigDB 数据库合并和去重后获得 EALMRGs。通过单因素 COX 回归分析筛选预后 EALMRGs，并基于这些基因通过最小绝对收缩和选择算子（LASSO）回归构建预后模型。然后在泛癌数据中验证 EALMRGs 的预后价值。通过时间特征 ROC 曲线分析评估预后基因的有效性。
根据预后高低风险组，我们鉴定出 5 个枢纽基因（ABCB1、CAP1、EGFR、PPARG、SNCA）。风险公式在另外 3 个胰腺癌患者队列中得到验证，并在泛癌数据中进行了探索。此外，低风险组中 T 细胞和树突状细胞浸润明显增加。在胰腺癌的单细胞测序数据中也鉴定出这 5 个枢纽基因，并有重要的途径。此外，基于胰腺癌数据的功能富集分析表明，蛋白丝氨酸/苏氨酸激酶活性、焦点黏附、肌动蛋白结合、细胞-基质连接、有机酸转运和转运体活性的调节与 EALMRGs 中基因的表达显著相关。
我们的风险公式在多种癌症中显示出潜在的预后价值，并在胰腺癌中表现出显著的免疫浸润和生物学途径改变。
