Early detection of PDAC remains challenging due to the lack of early symptoms and the absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics signatures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used Western blotting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal distributions were performed using one-way ANOVA followed by Tukey’s post hoc test, and pairwise tests were performed usingt-tests.p≤ 0.05 was considered statistically significant. Protein clusters of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium-binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166, and S100A13 as potential meaningful biomarker candidates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with the identifier PXD053169.
胰腺导管腺癌(PDAC)的早期检测因缺乏早期症状和可靠的生物标志物而面临挑战。本项目旨在识别能够区分伴有糖尿病(DM)的PDAC患者与非糖尿病PDAC患者的miRNA和蛋白质组学特征。研究采用蛋白质组学分析和miRNA芯片进行蛋白质及miRNA筛选,并利用蛋白质印迹法和实时定量逆转录聚合酶链反应(qRT-PCR)对蛋白质和miRNA进行验证。对于呈正态分布的实验组间比较,采用单因素方差分析结合Tukey事后检验,配对检验则使用t检验。p≤0.05被认为具有统计学显著性。蛋白质组学筛选检测到分化簇蛋白166(CD166)、糖蛋白CD63(CD63)、S100钙结合蛋白A13(S100A13)和肿瘤坏死因子-β(TNF-β)等蛋白簇。miRNA分析显示miRNA 1285存在差异性调控。通过蛋白质印迹法验证了先前报道的miR-1285靶蛋白:钙黏蛋白-1(CDH-1)、细胞Jun蛋白(c-Jun)、p53、果蝇母体抗背侧蛋白同源物4(Smad4)、人转谷氨酰胺酶2(TGM2)以及Yes相关蛋白(YAP)。通过qRT-PCR成功验证了miR-1285-3p在PDAC+DM患者中存在差异性调控。总体而言,我们的数据表明miRNA1285-3p、TGM2、CDH-1、CD166和S100A13可能成为表征PDAC+DM患者的有潜力的生物标志物。相关数据可通过ProteomeXchange获取,标识符为PXD053169。