Scientific Reports ( IF 3.8 ) Pub Date : 2023-10-31 , DOI: 10.1038/s41598-023-44646-x Chuan-Long Zhang 1 , Qian Shen 1 , Fu-Dong Liu 1 , Fan Yang 2 , Meng-Qi Gao 3 , Xiao-Chen Jiang 1 , Yi Li 1 , Xi-Yuan Zhang 2 , Ge-Er En 2 , Xue Pan 1, 4 , Bo Pang 5
The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package ‘limma.’ A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1high was enriched in interferon alpha (IFN-α) response and ITGA2high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy.
中文翻译:
SDC1 和 ITGA2 作为与 IPMN 相关的 PDAC 的新型预后生物标志物
现有的生物标志物不足以预测胰腺导管腺癌(PDAC)的预后。导管内乳头状粘液性肿瘤 (IPMN) 是 PDAC 的前兆;因此,从 PDAC 和 IPMN 的差异表达基因(DEG)中鉴定生物标志物是预测 PDAC 预后的一种新的可靠策略。在本研究中,从基因表达综合数据库下载了四个数据集,并使用 R 包“limma”进行标准化。总共分析了51个IPMN和81个PDAC样本,鉴定出PDAC和IPMN中的341个DEG; DEGs参与细胞外基质和肿瘤微环境。 SDC1和ITGA2证明了可接受的生存预后,它们在体外 PDAC 细胞增殖、凋亡和迁移过程中高表达。 SDC1高值在干扰素 α (IFN-α) 反应中富集,而ITGA2高值主要在上皮间质转化 (EMT) 中检测到,并使用蛋白质印迹法进行了验证。我们得出的结论是, SDC1和ITGA2是与 IPMN 相关的 PDAC 的潜在预后生物标志物。 PDAC 中SDC1和ITGA2表达的下调通过可能涉及 IFN-α 反应、EMT 和免疫调节的机制发生,这可能作为 PDAC 治疗的新靶点。