Serum levels of iCAF-derived Osteoglycin predict favorable outcome in pancreatic cancer. Serum levels of iCAF-derived Osteoglycin predict favorable outcome in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and -suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis in KPC mice indicated that OGN is derived from a subgroup of inflammatory CAFs. OGN-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts. Overall design: Examination of single cell RNA expression profiles of pancreatic cells and post induced pancreatitis

胰腺导管腺癌（Pancreatic ductal adenocarcinoma, PDAC）以丰富的间质为主要特征，其核心细胞组分为癌相关成纤维细胞（cancer-associated fibroblasts, CAFs）。近期研究明确解析了PDAC中CAF群体的异质性，证实间质中同时存在促瘤与抑瘤活性。本研究旨在鉴定可预示良好预后的CAF群体相关生物标志物。研究将骨聚糖蛋白（Osteoglycin, OGN）鉴定为候选血清预后标志物。对KPC小鼠开展的单细胞分析显示，OGN来源于一类炎性CAFs亚群。表达OGN的成纤维细胞与常驻健康胰腺星状细胞存在显著差异，并在胰腺炎发生过程中诱导产生。在两个独立的PDAC队列中，血清OGN水平可作为患者获得良好总体生存期的预后指标。总体实验设计：对胰腺细胞以及诱导型胰腺炎样本的单细胞RNA表达谱进行检测分析。