Guo Honglan, Fan Qinqiao
Department of Gastroenterology, The First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan, China.
Department of Hepatobiliary, The First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan, China.
Evid Based Complement Alternat Med. 2021 Jun 15;2021:5970085. doi: 10.1155/2021/5970085. eCollection 2021.
We aimed to investigate the expression of the hyaluronan-mediated motility receptor (HMMR) gene in hepatocellular carcinoma (HCC) and nonneoplastic tissues and to investigate the diagnostic and prognostic value of HMMR.
With the reuse of the publicly available The Cancer Genome Atlas (TCGA) data, 374 HCC patients and 50 nonneoplastic tissues were used to investigate the diagnostic and prognostic values of HMMR genes by receiver operating characteristic (ROC) curve analysis and survival analysis. All patients were divided into low- and high-expression groups based on the median value of HMMR expression level. Univariate and multivariate Cox regression analysis were used to identify prognostic factors. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of the HMMR genes involved in HCC. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC).
HMMR mRNA expression was significantly elevated in HCC tissues compared with that in normal tissues from both TCGA and the ICGC cohorts (all values <0.001). Increased HMMR expression was significantly associated with histologic grade, pathological stage, and survival status (all values <0.05). The area under the ROC curve for HMMR expression in HCC and normal tissues was 0.969 (95% CI: 0.948-0.983) in the TCGA cohort and 0.956 (95% CI: 0.932-0.973) in the ICGC cohort. Patients with high HMMR expression had a poor prognosis than patients with low expression group in both cohorts (all < 0.001). Univariate and multivariate analysis also showed that HMMR is an independent predictor factor associated with overall survival in both cohorts (all values <0.001). GSEA showed that genes upregulated in the high-HMMR HCC subgroup were mainly significantly enriched in the cell cycle pathway, pathways in cancer, and P53 signaling pathway.
HMMR is expressed at high levels in HCC. HMMR overexpression may be an unfavorable prognostic factor for HCC.
我们旨在研究透明质酸介导的运动受体（HMMR）基因在肝细胞癌（HCC）及非肿瘤组织中的表达情况，并探讨HMMR的诊断和预后价值。
利用公开可用的癌症基因组图谱（TCGA）数据，纳入374例HCC患者及50例非肿瘤组织，通过受试者工作特征（ROC）曲线分析和生存分析来研究HMMR基因的诊断和预后价值。所有患者根据HMMR表达水平的中位数分为低表达组和高表达组。采用单因素和多因素Cox回归分析来确定预后因素。进行基因集富集分析（GSEA）以探索HMMR基因参与HCC的潜在机制。在国际癌症基因组联盟（ICGC）的一个外部队列中进一步验证诊断和预后价值。
与TCGA和ICGC队列中的正常组织相比，HMMR mRNA在HCC组织中的表达显著升高（所有P值<0.001）。HMMR表达增加与组织学分级、病理分期及生存状态显著相关（所有P值<0.05）。在TCGA队列中，HCC组织与正常组织中HMMR表达的ROC曲线下面积为0.969（95%CI：0.948 - 0.983），在ICGC队列中为0.956（95%CI：0.932 - 0.973）。在两个队列中，HMMR高表达患者的预后均比低表达组患者差（所有P<0.001）。单因素和多因素分析还表明，HMMR是两个队列中与总生存相关的独立预测因素（所有P值<0.001）。GSEA显示，高HMMR HCC亚组中上调的基因主要显著富集于细胞周期途径、癌症途径和P53信号通路。
HMMR在HCC中高表达。HMMR过表达可能是HCC的不良预后因素。
