Zhang J, Chen J, Guan G W, Zhang T, Lu F M, Chen X M
Department of Microbiology & Infectious Disease Center, Peking University School of Basic Medical Sciences, Beijing 100191, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Jun 18;51(3):402-408. doi: 10.19723/j.issn.1671-167X.2019.03.005.
To explore the expression and clinical significance of chemokine CXCL10 and CXCR3 in hepatocellular carcinoma (HCC).
The expression and prognostic of CXCL10 and CXCR3 in HCC tumor tissues and non-tumor tissues were analyzed in two different publicly available databases the Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI). In addition, quantitative real-time PCR (qPCR) was used to detect the mRNA expression of CXCL10 and CXCR3 in 45 HCC clinical samples with HBV infection background. Pearson correlation and Spearman rank correlation were used to determine the correlation between the expression level of CXCL10 and CXCR3 in tumor and non-tumor tissues.
In TCGA database, the expression of CXCL10 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: 3.379±2.081 vs. 2.213±2.274, P<0.001; paired samples: 3.159±2.267 vs. 2.213±2.274, P=0.018). Similarly in LCI datebase (7.625±1.683 vs. 7.287±1.328, P=0.009). And higher CXCL10 expression was significantly associated with a better prognosis in the patients with HCC both in TCGA and LCI database (P=0.107, P=0.002). In TCGA database, the expression of CXCR3 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: -0.906±1.697 vs. -1.978±1.629, P<0.001; paired samples: -1.329±1.732 vs. -1.978±1.629, P=0.037), while lower in LCI database (3.989±0.339 vs. 4.074±0.309, P=0.003). In both databases, higher CXCR3 expression was significantly associated with a better prognosis in the HCC patients (P=0.004, P=0.014). Furthermore, in TCGA database, the expression level of CXCL10 and CXCR3 was positively correlated both in HCC tumor tissues and matched non-tumor tissues (r=0.584, P<0.001; r=0.776, P<0.001). The qPCR assay showed that the expression of CXCL10 in HBV-related HCC tumor tissues was significantly higher than those in normal liver tissues [0.479(0.223, 1.094) vs. 0.131(0.106, 0.159), P=0.010], and the expression in HBV-related non-tumor tissues was also significantly higher than those in normal liver tissues [0.484(0.241, 0.846) vs. 0.131(0.106, 0.159), P<0.001]. The same was true as CXCR3 [0.011(0.006, 0.019) vs. 0.002(0.001, 0.004), P=0.004; 0.016(0.011, 0.021) vs. 0.002(0.001, 0.004), P<0.001]. However there was no significant difference of CXCL10 and CXCR3 between tumor tissues and matched non-tumor tissues (P=1.000, P=0.374).
Expression of CXCL10 was up-regulated in HCC tissues, expression of CXCR3 was down-regulated in HBV-related HCC tissues, and the higher expression of both genes was correlated with better overall survival in HCC patients.
探讨趋化因子CXCL10和CXCR3在肝细胞癌（HCC）中的表达及其临床意义。
利用两个公开数据库癌症基因组图谱（TCGA）和肝癌研究所（LCI）分析HCC肿瘤组织和非肿瘤组织中CXCL10和CXCR3的表达及预后情况。此外，采用定量实时聚合酶链反应（qPCR）检测45例伴有HBV感染背景的HCC临床样本中CXCL10和CXCR3的mRNA表达。采用Pearson相关性分析和Spearman等级相关性分析确定肿瘤组织和非肿瘤组织中CXCL10和CXCR3表达水平之间的相关性。
在TCGA数据库中，HCC肿瘤组织中CXCL10的表达显著高于非肿瘤组织（非配对样本：3.379±2.081 vs. 2.213±2.274，P<0.001；配对样本：3.159±2.267 vs. 2.213±2.274，P=0.018）。在LCI数据库中情况类似（7.625±1.683 vs. 7.287±1.328，P=0.009）。在TCGA和LCI数据库中，较高的CXCL10表达均与HCC患者较好的预后显著相关（P=0.107，P=0.002）。在TCGA数据库中，HCC肿瘤组织中CXCR3的表达显著高于非肿瘤组织（非配对样本：-0.906±1.697 vs. -1.978±1.629，P<0.001；配对样本：-1.329±1.732 vs. -1.978±1.629，P=0.037），而在LCI数据库中则较低（3.989±0.339 vs. 4.074±0.309，P=0.003）。在两个数据库中，较高的CXCR3表达均与HCC患者较好的预后显著相关（P=0.004，P=0.014）。此外，在TCGA数据库中，HCC肿瘤组织和配对的非肿瘤组织中CXCL10和CXCR3的表达水平均呈正相关（r=0.584，P<0.001；r=0.776，P<0.001）。qPCR检测显示，HBV相关HCC肿瘤组织中CXCL10的表达显著高于正常肝组织[0.479(0.223, 1.094) vs. 0.131(0.106, 0.159)，P=0.010]，HBV相关非肿瘤组织中CXCL10的表达也显著高于正常肝组织[0.484(0.241, 0.846) vs. 0.131(0.106, 0.159)，P<0.001]。CXCR3情况相同[0.011(0.006, 0.019) vs. 0.002(0.001, 0.004)，P=0.004；0.016(0.011,
