皮肤恶性黑色素瘤组织中微小RNA-185-5p、SOX13的表达及临床意义

Expressions of microRNA-185-5p and SOX13 in skin malignant melanoma and their clinical significance

  • 摘要:
      目的  检测微小RNA-185-5p(miR-185-5p)和SOX13在皮肤恶性黑色素瘤(CMM)组织中的表达情况,并探讨其临床意义。
      方法  选择行手术治疗的61例CMM患者为观察对象(CMM组),另外,选择61例同时期诊断为皮肤良性色素痣的患者组织标本为对照组。根据miR-185-5p在CMM组织中表达水平,将CMM患者分为miR-185-5p高表达组(miR-185-5p表达水平≥0.47)31例和miR-185-5p低表达组(miR-185-5p表达水平 < 0.47)30例。根据SOX13蛋白在CMM组织中的表达结果,将CMM患者分为SOX13阳性表达组36例和SOX13阴性表达组25例。采用实时荧光定量聚合酶链式反应(qRT-PCR)法检测CMM组织与色素痣组织中miR-185-5p、SOX13 mRNA的表达水平,采用免疫组织化学法检测SOX13蛋白表达水平,采用Pearson法分析CMM组织中miR-185-5p与SOX13 mRNA表达水平的相关性,采用Kaplan-Meier生存曲线分析miR-185-5p、SOX13表达与CMM患者生存率的关系,采用Cox回归模型分析CMM患者的预后影响因素。
      结果  CMM组织中, miR-185-5p表达水平为(0.47±0.08), 低于色素痣组织的(1.01±0.13), 差异有统计学意义(t=27.630, P < 0.05); CMM组织中SOX13 mRNA的表达水平为(2.32±0.51), 高于色素痣组织的(1.05±0.11), 差异有统计学意义(t=19.012, P < 0.05); CMM组织中SOX13蛋白阳性表达率(59.02%)高于色素痣组织(13.11%), 差异有统计学意义(P < 0.05); CMM组织中miR-185-5p与SOX13 mRNA的表达呈负相关(r=-0.635, P < 0.05); CMM组织中, miR-185-5p、SOX13表达与浸润程度和淋巴结转移有关(P < 0.05); miR-185-5p高表达组3年生存率高于miR-185-5p低表达组,差异有统计学意义(χ2=5.871, P=0.015); SOX13阳性表达组3年生存率低于SOX13阴性表达组(χ2=5.030, P=0.020); 淋巴结转移、SOX13是CMM患者不良预后的独立危险因素,而miR-185-5p是CMM患者不良预后的保护因素(P < 0.05)。
      结论  CMM组织中miR-185-5p呈低表达, SOX13呈高表达,且两者的表达与CMM患者淋巴结转移等临床病理特征和预后有关,或可作为CMM潜在的预后标志物。

     

    Abstract:
      Objective  To detect the expressions of microRNA-185-5p (miR-185-5p) and SOX13 in cutaneous malignant melanoma (CMM) tissues, and to explore their clinical significance.
      Methods  A total of 61 CMM patients who underwent surgical treatment were selected as observation objects(CMM group), and another 61 tissue specimens diagnosed as benign pigmented nevi on the skin during the same period were selected as control group, according to the expression level of miR-185-5p in CMM tissues, CMM patients were divided into high miR-185-5p expression group(31 cases, miR-185-5p expression level ≥0.47) and low miR-185-5p expression group (30 cases, miR-185-5p expression level < 0.47). According to the results of SOX13 protein expression in CMM tissue, CMM patients were divided into SOX13 positive expression group (36 cases) and SOX13 negative expression group(25 cases). Quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) method to detect the expression levels of miR-185-5p and SOX13 mRNA in CMM tissues and pigmented nevus tissues; immunohistochemical method was used to detect the expression level of SOX13 protein; Pearson method was used to analyze the correlation between miR-185-5p and SOX13 mRNA expression levels in CMM tissues; Kaplan-Meier survival curve was used to analyze the relationshipof the expressions of miR-185-5p and SOX13 with the survival rate of CMM patients; Cox regression model was used to analyze the prognostic influencing factors of CMM patients.
      Results  The expression level of miR-185-5p in CMM tissue was (0.47±0.08), which was significantly lower than (1.01±0.13) in pigmented nevus tissue (t=27.630, P < 0.05); the expression level of SOX13 mRNA in CMM tissue was significantly higher than that in pigmented nevus tissue(2.32±0.51) versus (1.05±0.11), t=19.012, P < 0.05; the positive expression rate of SOX13 protein in CMM tissue was significantly higher than that in pigmented nevus tissue (59.02% versus 13.11%, P < 0.05); there was a negative correlation between miR-185-5p and SOX13 mRNA expression in CMM tissues (r=-0.635, P < 0.05); the expressions of miR-185-5p and SOX13 in CMM tissue were related to the degree of invasion and lymph node metastasis (P < 0.05); the 3-year survival rate of the miR-185-5p high expression group was significantly higher than that of miR-185-5p low expression group (χ2=5.871, P=0.015); the 3-year survival rate of the SOX13 positive expression group was significantly lower than that of the SOX13 negative expression group (χ2=5.030, P=0.020); lymph node metastasis and SOX13 were independent risk factors for poor prognosis of CMM patients (P < 0.05), and miR-185-5p was a protective factor for poor prognosis of CMM patients (P < 0.05).
      Conclusion  The expression of miR-185-5p is low and the expression of SOX13 is high in CMM tissues. They are related to clinicopathological characteristics (such as lymph node metastasis) and prognosis in CMM patients, and may be used as potential prognostic markers of CMM.

     

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