HMMR在肝细胞癌中的表达及其临床意义

Expression of HMMR in Hepatocellular Carcinoma and Its Clinical Significance

摘要: 目的：探讨透明质酸介导的运动性受体(HMMR)在肝细胞癌(HCC)中的表达特征及其临床意义，评估其与患者预后及免疫浸润的关系。方法：从TCGA数据库获取374例HCC样本的转录组数据及配对临床资料，分析HMMR在肿瘤组织与正常组织间的表达差异。采用Kaplan-Meier生存分析和Cox回归模型评估HMMR对总生存期(OS)的影响。通过Logistic回归探讨HMMR表达与临床病理特征的关系。进一步应用ssGSEA算法评估HMMR表达与24种肿瘤浸润免疫细胞的相关性。结果：HMMR在HCC中显著高表达，其高表达与T分期、临床分期等特征显著相关。HMMR高表达患者的OS明显缩短，且在多因素分析中，HMMR上调为独立的不良预后因素。此外，HMMR表达与多种免疫细胞的浸润显著相关，其中与Th2细胞、aDC呈正相关，与CD8+T细胞、pDC及细胞毒性细胞呈负相关。结论：HMMR在HCC中高表达并与预后不良相关，可作为潜在的预后生物标志物。其表达与免疫微环境密切相关，可能在肝癌免疫逃逸过程中发挥作用，为免疫治疗提供新的参考靶点。

Abstract: Objective: To investigate the expression pattern and clinical significance of hyaluronan-mediated motility receptor (HMMR) in hepatocellular carcinoma (HCC), and to evaluate its association with patient prognosis and immune cell infiltration. Methods: Transcriptome profiles and corresponding clinical information of 374 HCC cases were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression analysis was conducted to compare HMMR levels between tumor and normal tissues. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the impact of HMMR on overall survival (OS). Logistic regression was performed to explore the correlation between HMMR expression and clinicopathological characteristics. Single-sample gene set enrichment analysis (ssGSEA) was applied to quantify the infiltration levels of 24 immune cell subsets and evaluate their relationship with HMMR expression. Results: HMMR expression was significantly upregulated in HCC tissues compared with normal counterparts. High HMMR expression was strongly associated with advanced T stage and clinical stage. Patients with elevated HMMR levels exhibited significantly shorter OS, and multivariate Cox analysis identified HMMR upregulation as an independent predictor of poor prognosis. Furthermore, HMMR expression showed significant correlations with multiple immune cell types, displaying positive associations with Th2 cells and activated dendritic cells (aDC), and negative associations with CD8+ T cells, plasmacytoid dendritic cells (pDC), and cytotoxic cells. Conclusion: HMMR is highly expressed in HCC and is associated with unfavorable prognosis, serving as a potential biomarker for survival prediction. Its close relationship with immune infiltration suggests a role in regulating the immune microenvironment and contributing to immune evasion, providing a potential target for future immunotherapeutic interventions.