组氨酸三聚体核苷结合蛋白1在黑素瘤组织中的表达及其基因启动子甲基化水平研究

中华皮肤科杂志 ›› 2016, Vol. 49 ›› Issue (7): 478-481.

组氨酸三聚体核苷结合蛋白1在黑素瘤组织中的表达及其基因启动子甲基化水平研究

温斯健¹,²,倪娜娜³,张韡³,宋昊⁴,王小坡⁵,邵雪宝⁶,李阿梅⁷,程伟⁸,孙建方⁶

1. 广西医科大学第一附属医院皮肤性病科
2. 广西医科大学第一附属医院皮肤性病科（现在本所读研）
3. 中国医学科学院皮肤病研究所
4. 中国医学科学院南京皮肤病研究所
5. 中国医学科学院北京协和医学院皮肤病研究所
6. 南京中国医学科学院北京协和医学院皮肤病研究所
7. 南京市中国医学科学院皮肤病研究所
8. 中国医学科学院皮肤病医院

收稿日期:2015-11-09 修回日期:2016-02-19 发布日期:2016-06-30
通讯作者: 孙建方 E-mail:fangmin5758@aliyun.com
基金资助:
江苏省临床医学科技专项-医学研究中心项目;江苏省自然科学基金;2012年高等学校博士学科点专项科研基金

HINT1 protein and gene promoter methylation in melanoma tissue

Received:2015-11-09 Revised:2016-02-19 Published:2016-06-30
Supported by:
;Natural Science Foundation of Jiangsu Province

摘要/Abstract

摘要：

目的检测组氨酸三聚体核苷结合蛋白1（HINT1）在黑素瘤中的表达和HINT1基因启动子甲基化状态，探讨HINT1启动子甲基化与临床病理参数的关系。方法采用甲基化特异性PCR（MSP）法检测56例黑素瘤及瘤旁组织和51例色素痣组织中HINT1基因启动子区甲基化水平，免疫组化法检测56例黑素瘤和51例色素痣组织中HINT1蛋白的表达。结果 MSP显示，黑素瘤组织、瘤旁组织及色素痣组织中HINT1基因启动子区甲基化率分别为76.8%（43/56）、33.9%（19/56）和35.3%（18/51），黑素瘤组HINT1基因启动子区甲基化率明显高于瘤旁组织组和色素痣组，且差异有统计学意义（χ2 = 20.810、18.749，均P < 0.05），瘤旁组织组与色素痣组间差异无统计学意义（χ2 = 0.022，P > 0.05）。免疫组化显示，56例黑素瘤和51例色素痣组织中分别有12例（21.4%）和42例（82.4%）HINT1蛋白阳性表达，两组阳性率差异有统计学意义（χ2 = 39.633，P < 0.01）。12例HINT1蛋白阳性的黑素瘤组织中，有6例HINT1基因启动子甲基化，而在44例HINT1蛋白阴性的癌组织中HINT1启动子甲基化率高达84.1%（37/44），两组差异有统计学意义（χ2 = 6.147，P = 0.013）。56例黑素瘤中，HINT1基因启动子区甲基化率在Clark分级Ⅰ~Ⅱ级组（59.1%，13/22）与Ⅲ ~ Ⅴ级组（88.2%，30/34）间差异有统计学意义（χ2 = 6.365，P = 0.012）。结论 HINT1在黑素瘤组织中低表达，其机制可能与启动子区发生高甲基化有关；HINT1启动子区高甲基化可能参与黑素瘤的发生及发展。

Abstract:

Wen Sijian, Ni Nana, Zhang Wei, Song Hao, Wang Xiaopo, Shao Xuebao, Li Amei, Cheng Wei, Sun Jianfang Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Wen SJ, Zhang W, Song H, Wang XP, Shao XB, Li AM, Cheng W, Sun JF）; Central Laboratory, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Ni NN） Corresponding authors: Sun Jianfang, Email: fangmin5758@aliyun.com; Zhang Wei, Email: ifmtjoel@163.com 【Abstract】 Objective To measure histidine triad nucleotide?binding protein 1 （HINT1） protein and gene promoter methylation, and to analyze the relationship between HINT1 gene promoter methylation and clinical pathological features of melanoma. Methods Fifty?six patients with melanoma and 51 patients with nevus were enrolled as subjects and controls, respectively. Methylation?specific PCR （MSP） was performed to measure the methylation of HINT1 gene promoter in lesional and paratumoral tissue specimens from the patients with melanoma, as well as in lesional specimens from the patients with nevus. Immunohistochemistry was carried out to quantify the of HINT1 protein in these tissue specimens. Results MSP showed that the methylation rate of HINT1 gene promoter was significantly higher in melanoma tissues than in paratumoral and nevus tissues（76.8% ［43/56］ vs. 33.9%［19/56］ and 35.3%［18/51］, χ2 = 20.810 and 18.749, respectively, both P < 0.05）, but was insignificantly different between paratumoral and nevus tissues （χ2 = 0.022, P > 0.05）. Immunohistochemistry revealed that the rate of HINT1 was 21.4% （12/56） in melanoma tissues, compared to 82.4% （42/51） in nevus tissues （χ2 = 39.633, P < 0.01）. There was a significant difference in the methylation rate of HINT1 promoter between HINT1?positive and ?negative melanoma tissues （6/12 vs. 37/44 ［84.1%］, P < 0.05）, and between Clark level Ⅰ-Ⅱ and Ⅲ-Ⅴ melanoma tissues （59.1% ［13/22］ vs. 88.2% ［30/34］, χ2 = 6.365，P = 0.012）. Conclusions HINT1 protein is lowly expressed in melanoma, which may be associated with high methylation of its gene promoter. Moreover, the high methylation of HINT1 gene promoter may be involved in the initiation and progression of melanoma.

温斯健倪娜娜张韡宋昊王小坡邵雪宝李阿梅程伟孙建方. 组氨酸三聚体核苷结合蛋白1在黑素瘤组织中的表达及其基因启动子甲基化水平研究[J]. 中华皮肤科杂志, 2016,49(7):478-481. doi:

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