TMEM147与免疫浸润相关,可作为肝细胞癌的潜在预后生物标志物

IF 2.6 4区 医学 Q3 CELL BIOLOGY
Sheng Cheng, Jutang Li, Ming Xu, Qun Bao, Jiaoxiang Wu, Peng Sun, Bo Han
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引用次数: 0

摘要

背景:肝细胞癌(HCC)是最常见的恶性肿瘤之一,具有高死亡率。跨膜蛋白147 (TMEM147)是一种可介导免疫调节的七跨膜蛋白。然而,TMEM147与HCC免疫调节和HCC患者预后的相关性尚不清楚。方法:采用Wilcoxon秩和检验分析TMEM147在HCC中的表达。采用实时定量PCR (RT-qPCR)和Western blot分析肿瘤组织和细胞系,验证TMEM147在HCC中的表达。采用Kaplan-Meier分析、Cox回归分析和预后图评估TMEM147对HCC预后的影响。通过基因本体(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tmem147相关差异表达基因(DEGs)的功能。此外,我们利用单样本基因集富集分析(ssGSEA)和肝癌组织的免疫荧光染色检测了TMEM147表达与免疫浸润之间的关系。结果:我们的研究结果显示,TMEM147在人HCC组织中的表达明显高于邻近正常肝组织,在人HCC细胞系中也有类似的发现。TMEM147高表达与肝细胞癌的T分期、病理分期、组织学分级、种族、甲胎蛋白水平和血管浸润相关。此外,我们发现TMEM147的高表达与较短的生存时间相关,TMEM147可能是总生存期、T期、M期、病理期和肿瘤状态的危险因素。机制研究表明,TMEM147高表达与B淋巴细胞、抗原应答、il - 6信号通路、细胞周期、Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)信号通路和髓细胞瘤病癌基因(MYC)靶点有关。相应地,TMEM147的表达与肝癌中免疫细胞的浸润呈正相关,包括Th2细胞、滤泡辅助性T细胞、巨噬细胞和NK CD56亮细胞。结论:TMEM147可能是肝癌预后不良的生物标志物,与免疫细胞浸润有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TMEM147 Correlates with Immune Infiltration and Serve as a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

TMEM147 Correlates with Immune Infiltration and Serve as a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

TMEM147 Correlates with Immune Infiltration and Serve as a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

TMEM147 Correlates with Immune Infiltration and Serve as a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: TMEM147 might be a biomarker for poor prognosis and is related to immune cell infiltration in HCC.

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来源期刊
Analytical Cellular Pathology
Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY
CiteScore
4.90
自引率
3.10%
发文量
70
审稿时长
16 weeks
期刊介绍: Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.
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