Coto-Llerena Mairene, Ercan Caner, Kancherla Venkatesh, Taha-Mehlitz Stephanie, Eppenberger-Castori Serenella, Soysal Savas D, Ng Charlotte K Y, Bolli Martin, von Flüe Markus, Nicolas Guillaume P, Terracciano Luigi M, Fani Melpomeni, Piscuoglio Salvatore
Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland.
Visceral Surgery Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
Front Oncol. 2020 Jul 8;10:979. doi: 10.3389/fonc.2020.00979. eCollection 2020.
Fibroblast activation protein α (FAP) plays an important role in tissue remodeling and helps tumor cells invade surrounding tissue. We sought to investigate FAP as a prognostic molecular marker in colorectal cancer (CRC) using immunohistochemical and transcriptomic data. expression and clinicopathological information were obtained from The Cancer Genome Atlas data set. The association of expression and tissue cellular heterogeneity landscape was explored using the xCell method. We evaluated FAP protein expression in a cohort of 92 CRCs and 19 non-tumoral tissues. We observed that was upregulated in tumors both at the mRNA and protein levels, and its expression was associated with advanced stages, poor survival, and consensus molecular subtype 4. expression was also associated with angiogenesis and collagen degradation. We observed an enrichment in immune-cell process-related genes associated with overexpression. Colorectal cancers with high expression display an inflamed phenotype enriched for macrophages and monocytes. Those tumors showed enrichment for regulatory T cell populations and depletion of T1 and natural killer T cells, pointing to an immunosuppressive environment. Colorectal cancers with high levels of stromal FAP are associated with aggressive disease progression and survival. Our results suggest that FAP plays additional roles in tumor progression such as modulation of angiogenesis and immunoregulation in the tumor microenvironment.
成纤维细胞活化蛋白α（FAP）在组织重塑中起重要作用，并帮助肿瘤细胞侵袭周围组织。我们试图利用免疫组织化学和转录组数据研究FAP作为结直肠癌（CRC）的预后分子标志物。从癌症基因组图谱数据集中获取表达和临床病理信息。使用xCell方法探索表达与组织细胞异质性景观的关联。我们评估了92例CRC和19例非肿瘤组织中FAP蛋白的表达。我们观察到，在肿瘤中，其mRNA和蛋白水平均上调，其表达与晚期、不良生存和共识分子亚型4相关。表达还与血管生成和胶原蛋白降解相关。我们观察到与过表达相关的免疫细胞过程相关基因富集。高表达的结直肠癌表现出富含巨噬细胞和单核细胞的炎症表型。那些肿瘤显示调节性T细胞群体富集，T1和自然杀伤性T细胞耗竭，表明存在免疫抑制环境。基质FAP水平高的结直肠癌与侵袭性疾病进展和生存相关。我们的结果表明，FAP在肿瘤进展中发挥额外作用，如调节肿瘤微环境中的血管生成和免疫调节。
