Wang Xiangcheng, Niu Ruilong, Yang Hao, Lin Yu, Hou Hui, Yang Hong
Department of Nuclear Medicine, Shenzhen People's Hospital, Shenzhen, P.R. China.
Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, P.R. China.
Cell Biol Int. 2024 May;48(5):577-593. doi: 10.1002/cbin.12154. Epub 2024 Mar 19.
Fibroblast activation protein (FAP) has been indicated to express in cancer-associated fibroblasts (CAFs) in most cancers. This work was dedicated to exploring FAP's effects on hepatocellular carcinoma (HCC). The data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, ImmPort, and Reactome databases. The correlation between FAP and HCC patients' prognosis was explored via survival analysis. The qRT-PCR and western blot analysis were used to analyze the FAP mRNA and protein expression levels, respectively. The cell proliferation and apoptosis were determined using the cell counting kit-8 assay kit and Annexin V-FITC/PI apoptosis kit, respectively. The HCC patients with FAP overexpression displayed a worse prognosis. The FAP expression was positively associated with the infiltration levels of tumor purity, B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell. The optimal nine immune related genes were screened between two groups (FAP high vs. low). Moreover, we identified 24 energy metabolism related genes (FAP high vs. low) and these 24 genes were highly expressed in the high FAP expression group. The FAP expression had a significant positive correlation with the expression of PD-1, CTLA4, PDL-1, and PDL-2. The FAP overexpression promoted proliferation and migration while inhibiting the apoptosis of HCC cells. The FAP overexpression promoted the progression of HCC by regulating the immunity to affect the prognosis of HCC patients, thereby serving as a poor prognostic marker for HCC patients.
成纤维细胞活化蛋白（FAP）已被证实可在大多数癌症的癌症相关成纤维细胞（CAF）中表达。这项研究致力于探索FAP对肝细胞癌（HCC）的影响。数据取自癌症基因组图谱、基因表达综合数据库、免疫数据库和反应体数据库。通过生存分析探究FAP与HCC患者预后之间的相关性。分别采用qRT-PCR和蛋白质印迹分析来检测FAP的mRNA和蛋白表达水平。分别使用细胞计数试剂盒-8和膜联蛋白V-FITC/PI凋亡试剂盒检测细胞增殖和凋亡情况。FAP过表达的HCC患者预后较差。FAP表达与肿瘤纯度、B细胞、CD8 + T细胞、CD4 + T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈正相关。在两组（FAP高表达组与低表达组）之间筛选出了9个最佳免疫相关基因。此外，我们鉴定出了24个能量代谢相关基因（FAP高表达组与低表达组），这24个基因在FAP高表达组中高表达。FAP表达与PD-1、CTLA4、PDL-1和PDL-2的表达呈显著正相关。FAP过表达促进了HCC细胞的增殖和迁移，同时抑制其凋亡。FAP过表达通过调节免疫来影响HCC患者的预后，从而促进HCC的进展，因此可作为HCC患者预后不良的标志物。
