VCAN在乙型肝炎病毒诱导的肝细胞癌中高表达，是免疫检查点抑制剂的潜在生物标志物。
VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors.
作者信息
Wang Mu-Qi, Li Ya-Ping, Xu Meng, Tian Yan, Wu Yuan, Zhang Xin, Shi Juan-Juan, Dang Shuang-Suo, Jia Xiao-Li
机构信息
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
出版信息
World J Gastrointest Oncol. 2022 Oct 15;14(10):1933-1948. doi: 10.4251/wjgo.v14.i10.1933.
BACKGROUND
As a proteoglycan, VCAN exists in the tumor microenvironment and regulates tumor proliferation, invasion, and metastasis, but its role in hepatocellular carcinoma (HCC) has not yet been elucidated.
AIM
To investigate the expression and potential mechanism of action of VCAN in HCC.
METHODS
Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, we explored the correlation between VCAN expression and clinical features, and analyzed the prognosis of patients with high and low VCAN expression. The potential mechanism of action of VCAN was explored by Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis. We also explored immune cell infiltration, immune checkpoint gene expression, and sensitivity of immune checkpoint [programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA4)] inhibitor therapy in patients with different VCAN expression. VCAN mRNA expression and VCAN methylation in peripheral blood were tested in 100 hepatitis B virus (HBV)-related patients (50 HCC and 50 liver cirrhosis).
RESULTS
VCAN was highly expressed in HCC tissues, which was associated with a poor prognosis in HCC patients. No significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC, but there was a significant difference in VCAN methylation between the two groups. The correlation between VCAN and infiltrations of several different tumor immune cell types (including B cells, CD8 T cells, and eosinophils) was significantly different. VCAN was strongly related to immune checkpoint gene expression and tumor mutation burden, and could be a biomarker of sensitivity to immune checkpoint (PD1/CTLA4) inhibitors. In addition, VCAN mRNA expression was associated with hepatitis B e antigen, HBV DNA, white blood cells, platelets, cholesterol, and coagulation function.
CONCLUSION
High VCAN level could be a possible biomarker for poor prognosis of HCC, and its immunomodulatory mechanism in HCC warrants investigation.
背景
作为一种蛋白聚糖，VCAN存在于肿瘤微环境中，调节肿瘤的增殖、侵袭和转移，但其在肝细胞癌（HCC）中的作用尚未阐明。
目的
研究VCAN在HCC中的表达及潜在作用机制。
方法
基于癌症基因组图谱肝细胞癌数据集，我们探讨了VCAN表达与临床特征之间的相关性，并分析了VCAN高表达和低表达患者的预后。通过基因本体分析、京都基因与基因组百科全书分析和基因集富集分析来探索VCAN的潜在作用机制。我们还探讨了不同VCAN表达患者的免疫细胞浸润、免疫检查点基因表达以及免疫检查点[程序性细胞死亡蛋白1（PD-1）/细胞毒性T淋巴细胞抗原4（CTLA4）]抑制剂治疗的敏感性。检测了100例乙型肝炎病毒（HBV）相关患者（50例HCC和50例肝硬化）外周血中的VCAN mRNA表达和VCAN甲基化情况。
结果
VCAN在HCC组织中高表达，这与HCC患者的不良预后相关。HBV相关肝硬化患者和HCC患者血液中VCAN mRNA表达无显著差异，但两组之间VCAN甲基化存在显著差异。VCAN与几种不同肿瘤免疫细胞类型（包括B细胞、CD8 T细胞和嗜酸性粒细胞）的浸润之间的相关性显著不同。VCAN与免疫检查点基因表达和肿瘤突变负荷密切相关，可能是免疫检查点（PD1/CTLA4）抑制剂敏感性的生物标志物。此外，VCAN mRNA表达与乙肝e抗原、HBV DNA、白细胞、血小板、胆固醇和凝血功能相关。
结论
高VCAN水平可能是HCC预后不良的一个潜在生物标志物，其在HCC中的免疫调节机制值得研究。
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