癌相关成纤维细胞（CAFs）在肿瘤基质中沉积和重塑胶原蛋白，影响癌症进展和治疗效果。CAFs是新型治疗药物的焦点，旨在使肿瘤微环境正常化。为了做到这一点，需要更好地了解癌症中CAF的异质性和胶原蛋白的组成。在本研究中，我们旨在通过对多个水平的胶原蛋白表达进行概述，以便确定癌症生物标志物。我们使用公开可获得的胰腺导管腺癌单细胞RNA测序（RNA-seq）数据集，调查了各种细胞类型和CAF亚型中的胶原蛋白表达模式。接下来，我们调查了癌症基因组图谱（TCGA）数据库中不同癌症类型的肿瘤样本中的胶原蛋白表达情况，并评估了特定胶原蛋白表达模式与预后的关系。最后，我们使用免疫分析面板对癌症患者血清中的胶原蛋白片段进行了概述。我们发现胰星状细胞和成纤维细胞是胰腺中胶原蛋白的主要产生者。所有CAF亚型中均表达COL1A1、COL3A1、COL5A1和COL6A1，而COL8A1、COL10A1、COL11A1和COL12A1仅特异地表达于肌成纤维细胞CAF（myCAF），COL14A1仅特异地表达于炎症性CAF（iCAF）。在TCGA数据库中，肿瘤相对于固性肿瘤类型下myCAF胶原蛋白COL10A1和COL11A1表达升高，并发现了高表达与较差生存率之间的多个关联。最后，相对于健康对照组，患者血清中循环胶原蛋白生物标志物升高，其中COL11A1（myCAF）是最佳的诊断准确性标志物。总之，CAF以非规范的胶原蛋白表达谱，特定的胶原蛋白亚型与PDAC中的iCAF和myCAF相关。在不同固性肿瘤中，这些胶原蛋白在细胞、肿瘤和全身水平上被失调，并与生存率相关。这些发现可能带来新的发现，例如新的生物标志物和治疗靶点。© 2023 作者。《病理学杂志》由约翰·威利有限公司代表大不列颠和爱尔兰病理学学会出版。

Cancer-associated fibroblasts (CAFs) deposit and remodel collagens in the tumor stroma, impacting cancer progression and efficacy of interventions. CAFs are the focus of new therapeutics with the aim of normalizing the tumor microenvironment. To do this, a better understanding of CAF heterogeneity and collagen composition in cancer is needed. In this study, we sought to profile the expression of collagens at multiple levels with the goal of identifying cancer biomarkers. We investigated the collagen expression pattern in various cell types and CAF subtypes in a publicly available single-cell RNA sequencing (RNA-seq) dataset of pancreatic ductal adenocarcinoma. Next, we investigated the collagen expression profile in tumor samples across cancer types from The Cancer Genome Atlas (TCGA) database and evaluated if specific patterns of collagen expression were associated with prognosis. Finally, we profiled circulating collagen peptides using a panel of immunoassays to measure collagen fragments in the serum of cancer patients. We found that pancreatic stellate cells and fibroblasts were the primary producers of collagens in the pancreas. COL1A1, COL3A1, COL5A1, COL6A1 were expressed in all CAF subtypes, whereas COL8A1, COL10A1, COL11A1, COL12A1 were specific to myofibroblast CAFs (myCAF) and COL14A1 specific to inflammatory CAFs (iCAF). In TCGA database, myCAF collagens COL10A1 and COL11A1 were elevated across solid tumor types, and multiple associations between high expression and worse survival were found. Finally, circulating collagen biomarkers were elevated in the serum of patients with cancer relative to healthy controls with COL11A1 (myCAF) having the best diagnostic accuracy of the markers measured. In conclusion, CAFs express a noncanonical collagen profile with specific collagen subtypes associated with iCAFs and myCAFs in PDAC. These collagens are deregulated at the cellular, tumor, and systemic levels across different solid tumors and associate with survival. These findings could lead to new discoveries such as novel biomarkers and therapeutic targets. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.