胰腺导管腺癌（PDAC）的特征性纤维化基质源自进行性组织硬化，诱导上皮间质转化和转移性播散。本研究的目的是通过分析 PDAC 衍生的细胞外囊泡 (EV) 的蛋白质组来研究基质硬度对 PDAC 进展的影响。 PDAC 细胞系（mPDAC 和 KPC）在硬度接近非肿瘤（NT）或肿瘤组织（T）的合成支持物上生长，并通过定量 MSE 无标记分析细胞来源的 EV 中的蛋白质表达水平质谱方法。我们的分析找出了 mPDAC-EV 中的 15 个差异表达蛋白 (DEP) 和 KPC-EV 中的 20 个 DEP，以响应基质刚性。上调的蛋白质参与代谢、基质重塑和免疫反应的过程，这些都是 PDAC 进展的标志。多模态网络分析显示，大多数 DEP 与胰腺癌密切相关。有趣的是，在 DEP 中，mPDAC-EV 有 11 个相关基因（ACTB/ANXA7/C3/IGSF8/LAMC1/LGALS3/PCD6IP/SFN/TPM3/VARS/YWHAZ）和 9 个（ACTB/ALDH2/GAPDH/HNRNPA2B/ITGA2/NEXN/根据基因表达谱相互作用分析 (GEPIA)，KPC-EV 的 PKM/RPN1/S100A6) 在肿瘤组织中显着过表达。关于这些数据的潜在临床相关性，ACTB、ITGA2、GAPDH 和 PKM 基因簇对 PDAC 患者的总生存期显示出不利影响 (p < 0.05)。© 2024 Wiley‐VCH GmbH。

The fibrotic stroma characterizing pancreatic ductal adenocarcinoma (PDAC) derives from a progressive tissue rigidification, which induces epithelial mesenchymal transition and metastatic dissemination. The aim of this study was to investigate the influence of matrix stiffness on PDAC progression by analyzing the proteome of PDAC-derived extracellular vesicles (EVs). PDAC cell lines (mPDAC and KPC) were grown on synthetic supports with a stiffness close to non-tumor (NT) or tumor tissue (T), and the protein expression levels in cell-derived EVs were analyzed by a quantitative MSE label-free mass spectrometry approach. Our analysis figured out 15 differentially expressed proteins (DEPs) in mPDAC-EVs and 20 DEPs in KPC-EVs in response to matrix rigidification. Up-regulated proteins participate to the processes of metabolism, matrix remodeling, and immune response, altogether hallmarks of PDAC progression. A multimodal network analysis revealed that the majority of DEPs are strongly related to pancreatic cancer. Interestingly, among DEPs, 11 related genes (ACTB/ANXA7/C3/IGSF8/LAMC1/LGALS3/PCD6IP/SFN/TPM3/VARS/YWHAZ) for mPDAC-EVs and 9 (ACTB/ALDH2/GAPDH/HNRNPA2B/ITGA2/NEXN/PKM/RPN1/S100A6) for KPC-EVs were significantly overexpressed in tumor tissues according to gene expression profiling interaction analysis (GEPIA). Concerning the potential clinical relevance of these data, the cluster of ACTB, ITGA2, GAPDH and PKM genes displayed an adverse effect (p < 0.05) on the overall survival of PDAC patients.© 2024 Wiley‐VCH GmbH.