透明质酸介导的运动受体高表达预示不良预后：头颈部鳞状细胞癌的潜在治疗靶点

High Expression of Hyaluronan-Mediated Motility Receptor Predicts Adverse Outcomes: A Potential Therapeutic Target for Head and Neck Squamous Cell Carcinoma.

作者信息

Lu Tianzhu, Zheng Yahan, Gong Xiaochang, Lv Qiaoli, Chen Junjun, Tu Ziwei, Lin Shaojun, Pan Jianji, Guo Qiaojuan, Li Jingao

机构信息

Department of Radiation Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.

National Health Commission (NHC) Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma (Jiangxi Cancer Hospital of Nanchang University), Nanchang, China.

出版信息

Front Oncol. 2021 Mar 8;11:608842. doi: 10.3389/fonc.2021.608842. eCollection 2021.

DOI:10.3389/fonc.2021.608842

PMID:33763352

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7982417/

Abstract

Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC). Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR. HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue ( < 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169-2.266, = 0.004) and GSE41613 data (HR = 2.238, = 0.013). The methylation level of HMMR negatively correlated with the HMMR expression ( = -0.12, < 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation ( < 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed that expression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288, = 0.045) and progression-free survival (HR = 2.247, = 0.038) in 70 HNSCC. This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.

摘要

多项研究表明，透明质酸介导的运动受体（HMMR）在多种癌症中过表达，可能是一个潜在的预后因素。然而，仍需要进一步研究来确定HMMR在头颈部鳞状细胞癌（HNSCC）中的预后价值和潜在功能。从癌症基因组图谱数据库（TCGA）和基因表达综合数据库收集转录组表达数据，分析正常组织和肿瘤组织中HMMR表达的差异。通过cBioPortal分析HMMR甲基化水平与其mRNA表达之间的相关性。此外，使用MethSurv分析从TCGA获得的数据，以确定HMMR甲基化水平在HNSCC中的预后价值。采用基因集富集分析（GSEA）和单样本GSEA（ssGSEA）来探索HMMR的潜在生物学功能。与正常组织相比，HMMR在HNSCC肿瘤组织中高表达（<0.001）。多变量分析（MAV）显示，高HMMR mRNA表达是TCGA（HR = 1.628，95%CI：1.169 - 2.266， = 0.004）和GSE41613数据（HR = 2.238， = 0.013）中总生存期（OS）的独立预后因素。HMMR的甲基化水平与HMMR表达呈负相关（ = -0.12，<0.001），HMMR甲基化水平低的患者的OS比甲基化水平高的患者更差（<0.001）。GSEA发现HMMR表达与KARS、EMT和G2M检查点通路以及干扰素-γ和干扰素-α反应相关联，而ssGSEA显示表达与Th2细胞浸润水平呈正相关。MAV证实，在70例HNSCC中，高HMMR蛋白表达是OS（HR = 2.288， = 0.045）和无进展生存期（HR = 2.247， = 0.038）的不良独立因素。本研究表明，HNSCC中HMMR mRNA和蛋白的上调是预后不良的生物标志物。HMMR的生物学功能可能与KARS、EMT和G2M检查点通路以及干扰素-γ和干扰素-α反应有关。这些发现有助于阐明HMMR在致癌过程中的作用，并为进一步研究奠定基础。