5-羟甲基胞嘧啶表达与黑素瘤侵袭、转移、预后的相关性分析

Correlation analysis between the expression of 5-hydroxymethyl-cytosine and invasion, metastasis and prognosis of melanoma

目的 检测5-羟甲基胞嘧啶（5-hmc）在黑素瘤组织中的表达水平，分析5-hmc与黑素瘤侵袭、转移、预后的相关性。方法 采用免疫组化SP法检测5-hmc在67例黑素瘤、20例色素痣组织标本中的表达，采用Cox比例风险回归模型进行单因素和多因素回归分析5-hmc表达与黑素瘤患者预后的相关关系。结果 黑素瘤中5-hmc表达阳性率为40.30%（27/67），色素痣为75%（15/20），两组间差异有统计学意义（χ^2 = 7.428，P = 0.006）。美国癌症联合会临床分期Ⅳ期黑素瘤中5-hmc表达水平明显低于Ⅱ、Ⅲ期黑素瘤（χ^2 = 4.416，P = 0.036），淋巴结转移患者5-hmc表达水平明显低于无淋巴结转移患者（χ^2 = 5.902，P = 0.015），且5-hmc表达水平随黑素瘤组织Clark分级升高而降低（χ^2 = 4.828，P = 0.028）。5-hmc表达水平在不同年龄、性别、民族黑素瘤患者之间分布差异无统计学意义（P 〉 0.05）。Cox回归模型多因素分析显示，存在远处淋巴结转移（风险比：2.67，95% CI：1.22 - 5.84）、未手术切除（风险比：0.41，95% CI：0.18 - 0.95）、5-hmc低水平表达（风险比：3.54，95% CI：1.09 - 11.43）为预后不良的独立影响因素。结论 5-hmc可能参与黑素瘤侵袭转移，与黑素瘤预后相关。

Objective To detect the level of 5-hydroxymethyl-cytosine（5-hmc）in melanoma tissues, and to analyze the correlation between 5-hmc and the invasion, metastasis and prognosis of melanoma. Methods A streptavidin-peroxidase immunohistochemical method was used to detect the level of 5-hmc in 67 melanoma tissues and 20 pigmented nevi tissues. Univariate and multivariate analyses were performed with the Cox′s proportional hazards regression model to analyze the correlation between the of 5-hmc and the prognosis of melanoma. Results The rate of 5-hmc was significantly lower in melanoma tissues than in pigmented nevus tissues （40.30%[27/67] vs. 75%[15/20], χ^2 = 7.428, P = 0.006）. According to American Joint Committee on Cancer （AJCC） TNM staging system, the level of 5-hmc was significantly lower in the stage Ⅳmelanoma tissues than in the stage Ⅱ and stage Ⅲ melanoma tissues （χ^2 = 4.416, P = 0.036）. Patients with lymph node metastasis showed significantly lower of 5-hmc compared with those without lymph node metastasis （χ^2 = 5.902, P = 0.015）, and the level of 5-hmc significantly decreased along with the increase of Clark grade （χ^2 = 4.828, P = 0.028）. There were no significant differences in the level of 5-hmc between patients of different ages, genders or nationalities （P 〉 0.05）. Multivariate Cox regression analysis showed that distant lymph node metastasis （HR： 2.67, 95% CI： 1.22 - 5.84）, not receiving surgical resection （HR： 0.41, 95% CI： 0.18 - 0.95）, and low of 5-hmc（HR： 3.54, 95% CI： 1.09 - 11.43）were independent risk factors for poor prognosis of melanoma. Conclusion 5-Hmc may participate in the invasion and metastasis of melanoma, and be associated with the prognosis of melanoma.