Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Anal Cell Pathol (Amst). 2023 Jun 3;2023:4413049. doi: 10.1155/2023/4413049. eCollection 2023.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and is associated with high mortality. Transmembrane protein 147 (TMEM147) is a seven-transmembrane protein that may mediate immune regulation. However, the relevance of TMEM147 to immune regulation in HCC and the prognosis of HCC patients are unclear.
We analyzed TMEM147 expression in HCC by using the Wilcoxon rank-sum test. Real time quantitative PCR (RT-qPCR) and Western blot analysis of tumor tissues and cell lines were used to verify TMEM147 expression in HCC. The influence of TMEM147 on HCC prognosis was assessed using Kaplan-Meier analysis, Cox regression analysis, and a prognostic nomogram. The functions of the TMEM147-related differentially expressed genes (DEGs) were identified by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and gene set enrichment analysis (GSEA). In addition, we examined the associations between TMEM147 expression and immune infiltration using single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence staining of HCC tissues.
Our results showed that the expression of TMEM147 was significantly higher in human HCC tissues than in adjacent normal liver tissues, with similar findings in human HCC cell lines. High TMEM147 expression was correlated with T stage, pathological stage, histological grade, race, alpha-fetoprotein level, and vascular invasion in HCC. Moreover, we revealed that high TMEM147 expression was associated with shorter survival times and that TMEM147 could be a risk factor for overall survival, along with T stage, M stage, pathological stage, and tumor status. Mechanistic studies revealed that high TMEM147 expression was linked to the B lymphocyte, antigen response, IL6 signaling pathway, cell cycle, Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling pathway, and myelocytomatosis oncogene (MYC) targets. Correspondingly, TMEM147 expression was positively associated with the infiltration of immune cells, including Th2 cells, follicular helper T cells, macrophages, and NK CD56 bright cells in HCC.
TMEM147 might be a biomarker for poor prognosis and is related to immune cell infiltration in HCC.
肝细胞癌（HCC）是最常见的恶性肿瘤之一，死亡率很高。跨膜蛋白 147（TMEM147）是一种七跨膜蛋白，可能介导免疫调节。然而，TMEM147 与 HCC 中的免疫调节以及 HCC 患者的预后的相关性尚不清楚。
我们使用 Wilcoxon 秩和检验分析 HCC 中的 TMEM147 表达。使用实时定量 PCR（RT-qPCR）和 Western blot 分析肿瘤组织和细胞系来验证 HCC 中的 TMEM147 表达。使用 Kaplan-Meier 分析、Cox 回归分析和预后列线图评估 TMEM147 对 HCC 预后的影响。通过基因本体论（GO）/京都基因与基因组百科全书（KEGG）富集分析和基因集富集分析（GSEA）鉴定与 TMEM147 相关的差异表达基因（DEGs）的功能。此外，我们使用单样本基因集富集分析（ssGSEA）和 HCC 组织的免疫荧光染色检查 TMEM147 表达与免疫浸润之间的关联。
我们的结果表明，TMEM147 在人 HCC 组织中的表达明显高于相邻正常肝组织，在人 HCC 细胞系中也有类似的发现。高 TMEM147 表达与 HCC 中的 T 分期、病理分期、组织学分级、种族、甲胎蛋白水平和血管侵犯有关。此外，我们发现高 TMEM147 表达与较短的生存时间相关，并且 TMEM147 可以成为总生存的危险因素，与 T 分期、M 分期、病理分期和肿瘤状态一起。机制研究表明，高 TMEM147 表达与 B 淋巴细胞、抗原反应、IL6 信号通路、细胞周期、Kirsten 大鼠肉瘤病毒致癌基因同源物（KRAS）信号通路和髓系细胞瘤癌基因（MYC）靶标有关。相应地，TMEM147 表达与 HCC 中免疫细胞的浸润呈正相关，包括 Th2 细胞、滤泡辅助 T 细胞、巨噬细胞和 NK CD56 明亮细胞。
TMEM147 可能是预后不良的生物标志物，与 HCC 中的免疫细胞浸润有关。
