TIMP-3基因甲基化与结直肠癌临床病理的关系

Methylation of TIMP-3 gene and their relationships with their clinical-pathological characteristics of colorectal cancers

目的:探讨TIMP-3基因甲基化与结直肠癌临床病理指标和转移复发的关系。方法:采用巢式甲基化特异性PCR技术(NMSP法)检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3基因甲基化;采用RT-PCR 检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3 MRNA的表达。结果:肿瘤组织TIMP-3 MRNA的表达阳性率为64％,肿瘤组织TIMP-3 MRNA的表达率明显低于癌旁非癌组织(P<0．01);TIMP-3 MRNA的表达率无淋巴结转移组(34/42)高于淋巴结转移组(30/58)(P<0．01),甲基化阳性率DUKE’S C+D期伴淋巴结转移组明显高于 DUKE’S A+B期不伴淋巴结转移组(P<0．05)。结肠近端、分化程度差的结直肠癌组织甲基化阳性率明显高于远端直肠和分化程度高者(P<0．05)。结论:TIMP-3基因甲基化容易发生在结肠近端、DUKE’S C、D期、伴淋巴结转移、细胞分化差和浸润型结直肠癌患者。

AIM： To investigate whether methylation of the TIMP- 3 gene is associated with clinical - pathological characteristics, recun＇cnce and metastasis of the colorectal cancer. METHODS： Nest methylation specific PCR （nMSP） and RT- PCR techniques were used to detect methylation of TIMP - 3 gene and its mRNA expression in the colorectal cancer＇ specimen and adjacent non - cancerous tissues. RESULTS： The expression of TIMP - 3 mRNA in tumor tissues was distinctly reduced （ P 〈 0.01 ）. The expression of TIMP- 3 mRNA in those without lymph node metastasis was higher than those with lymph node metastasis （ P 〈 0.01 ）. The patients with Duke＇ s C, D and lymph nede metastasis were more to contain methylated TIMP - 3 compared to those with Duke＇s A, B and no lymph node metastasis （ P 〈 0.05）. Statistical differences in pathological characteristics such as tumor site, Duke＇s stage, histological differentiation and type between TIMP- 3 methylation positive group and negative group were observed （ P 〈 0.05 ）. CONCLUSION ： Methylation of the TIMP - 3 gene promoter usually occurs in the proximal site, infiltrating type, poor cellular differentiation, lymph node metastasis and advanced stage of colorectal cancers patients.