癌相关成纤维细胞的特定亚型与可切除性胰腺导管腺癌的较差生存率相关。
Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma.
作者信息
Knipper Karl, Damanakis Alexander I, Zhao Yue, Bruns Christiane J, Schmidt Thomas, Popp Felix C, Quaas Alexander, Lyu Su Ir
机构信息
Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany.
Institute of Pathology, University Hospital of Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany.
出版信息
Cancers (Basel). 2023 Mar 30;15(7):2049. doi: 10.3390/cancers15072049.
PURPOSE
The pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer entities. Effective therapy options are still lacking. The tumor microenvironment possibly bears further treatment possibilities. This study aimed to describe the expression patterns of four established carcinoma-associated fibroblast (CAFs) markers and their correlation in PDAC tissue samples.
METHODS
This project included 321 patients with PDAC who underwent surgery with a curative intent in one of the PANCALYZE study centers. Immunohistochemical stainings for FAP, PDGFR, periostin, and SMA were performed. The expression patterns of each marker were divided into low- and high-expressing CAFs and correlated with patients' survival.
RESULTS
Tumors showing SMA-, PeriostinSMA-, or PeriostinSMAPDGFRFAP-positive CAFs demonstrated significantly worse survival. Additionally, a high expression of SMA in PDAC tissue samples was shown to be an independent risk factor for worse survival.
CONCLUSION
This project identified three subgroups of PDAC with different expression patterns of CAF markers which showed significantly worse survival. This could be the base for the further characterization of the fibroblast subgroups in PDAC and contribute to the development of new targeted therapy options against CAFs.
目的
胰腺导管腺癌（PDAC）是最致命的癌症类型之一。目前仍缺乏有效的治疗方案。肿瘤微环境可能蕴含更多治疗潜力。本研究旨在描述四种已确定的癌相关成纤维细胞（CAF）标志物在PDAC组织样本中的表达模式及其相关性。
方法
该项目纳入了321例在PANCALYZE研究中心之一接受根治性手术的PDAC患者。对FAP、PDGFR、骨膜蛋白和平滑肌肌动蛋白（SMA）进行免疫组织化学染色。将每种标志物的表达模式分为低表达和高表达CAF，并与患者的生存率相关联。
结果
显示平滑肌肌动蛋白、骨膜蛋白-平滑肌肌动蛋白或骨膜蛋白-平滑肌肌动蛋白-PDGFR-FAP阳性CAF的肿瘤患者生存率显著较差。此外，PDAC组织样本中平滑肌肌动蛋白的高表达被证明是生存率较差的独立危险因素。
结论
本项目确定了三个PDAC亚组，其CAF标志物表达模式不同，生存率显著较差。这可能是进一步表征PDAC中成纤维细胞亚组的基础，并有助于开发针对CAF的新靶向治疗方案。
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