TYRP1、ABCB5 和 MMP17 在鼻腔鼻窦黏膜黑色素瘤中的表达及临床意义。
Expression and clinical significance of TYRP1, ABCB5, and MMP17 in sinonasal mucosal melanoma.
机构信息
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Institute of Otorhinolaryngology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
出版信息
Cancer Biomark. 2022;35(3):331-342. doi: 10.3233/CBM-220093.
BACKGROUND
Sinonasal mucosal melanoma (SNMM) is a lethal malignancy with poor prognosis. Treatment outcomes of SNMM are poor. Novel prognostic or progression markers are needed to help adjust therapy.
METHODS
RNA-seq was used to analyze the mRNA expression of tumor tissues and normal nasal mucosa from primary SNMM patients (n= 3). Real-time fluorescent quantitative PCR (qRT-PCR) was used to validate the results of RNA-seq (n= 3), while protein expression was analyzed by immunohistochemistry (IHC, n= 31) and western blotting (n= 3). Retrospective studies were designed to determine the clinical parameters and the total survival rate, and correlation between the protein expression levels of the most significant key genes and prognosis was analyzed.
RESULTS
In total, 668 genes were upregulated and 869 genes were downregulated in SNMM (fold change ⩾ 2, adjusted p value < 0.01). Both mRNA and protein expression levels of the key genes in SNMM tumor tissues were higher than those in the normal control nasal mucosal tissues. The expression rates of TYRP1, ABCB5, and MMP17 in 31 primary SNMM cases were 90.32%, 80.65%, and 64.52%, respectively. In addition, age, typical symptoms, and AJCC stage were related to overall survival rate of patients with SNMM (p< 0.05). Furthermore, the expression of ABCB5 was age-related (p= 0.002). Compared with individuals with negative ABCB5 expression, those with positive expression exhibited significantly poor overall survival (p= 0.02).
CONCLUSION
The expression levels of TYRP1, ABCB5, and MMP17 were significantly upregulated in SNMM tissues, and the expression of ABCB5 was related to poor prognosis in SNMM. Thus, ABCB5 may serve as a progression marker and can predict unfavorable prognosis in patients with SNMM.
背景
鼻腔鼻窦黑色素瘤（sinonasal mucosal melanoma，SNMM）是一种预后不良的致命恶性肿瘤。SNMM 的治疗效果较差，需要新的预后或进展标志物来帮助调整治疗方案。
方法
采用 RNA 测序分析了 3 例原发性 SNMM 患者肿瘤组织和正常鼻黏膜的 mRNA 表达情况。实时荧光定量 PCR（real-time fluorescent quantitative PCR，qRT-PCR）验证了 RNA 测序的结果（n=3），同时采用免疫组织化学（immunohistochemistry，IHC，n=31）和蛋白质印迹法（western blotting，n=3）分析了蛋白质表达情况。设计回顾性研究来确定临床参数和总生存率，并分析最显著关键基因的蛋白表达水平与预后之间的相关性。
结果
SNMM 中共有 668 个基因上调，869 个基因下调（fold change ⩾ 2，调整后的 p 值 < 0.01）。SNMM 肿瘤组织中关键基因的 mRNA 和蛋白表达水平均高于正常对照鼻黏膜组织。31 例原发性 SNMM 病例中 TYRP1、ABCB5 和 MMP17 的表达率分别为 90.32%、80.65%和 64.52%。此外，年龄、典型症状和 AJCC 分期与 SNMM 患者的总生存率相关（p<0.05）。此外，ABCB5 的表达与年龄相关（p=0.002）。与 ABCB5 表达阴性者相比，表达阳性者的总生存率显著较差（p=0.02）。
结论
TYRP1、ABCB5 和 MMP17 在 SNMM 组织中的表达水平显著上调，ABCB5 的表达与 SNMM 的不良预后相关。因此，ABCB5 可能作为一个进展标志物，预测 SNMM 患者预后不良。
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