Genetic oncological and molecular epidemiological research on development and progression of the biliary tract cancer in Asia

亚洲胆道癌发生和进展的遗传肿瘤学和分子流行病学研究

基本信息

批准号：
12576002
负责人：
MIWA Masanao
金额：
$ 6.59万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis.The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. To elucidate cytogenetic, we analyzed DNA copy number abnormalities of these cancers in genome-wide scale by comparative genomic hybridization. Poorly-differentiated carcinomas have more frequent chromosomal gain at 18p11 than well-differentiated carcinomas. Frequent decrease in copy number were observed at 1pter-p36 (34%) and 21q13-qter (28%). Alterations found in this study might be candidate for novel genes and prognostic factors in the intrahepatic bile duct cancer with chronic inflammation. We also found that the microsatellite instability (MSI) of intrahepatic cholangiocarcinoma in Thailand, was classified as low frequency MSI and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.

分别评估胆囊癌、慢性胆囊炎、黄色肉芽肿性胆囊炎(XGC)和正常胆囊上皮和间质中COX的表达。正常胆囊上皮中COX-2的表达率显着高于基质中。非癌癌灶邻近上皮中COX-2的表达率不仅显着低于癌症，而且慢性胆囊炎、XGC和正常胆囊的表达率也显着低于正常胆囊。在基质中，癌症、慢性胆囊炎和XGC中COX-2的表达率显着高于正常胆囊。非癌性邻近间质中癌的发生率明显低于癌和XGC。我们的研究结果表明，胆囊中COX-2的表达可能受到多种因素的调节，并且与癌发生没有直接关系。肝吸虫感染相关的肝内胆管癌（ICC）是泰国东北部的主要肝癌。为了阐明细胞遗传学，我们通过比较基因组杂交在全基因组范围内分析了这些癌症的 DNA 拷贝数异常。低分化癌比高分化癌在 18p11 处有更频繁的染色体增益。在 1pter-p36 (34%) 和 21q13-qter (28%) 观察到拷贝数频繁减少。这项研究中发现的改变可能是伴有慢性炎症的肝内胆管癌的新基因和预后因素的候选者。我们还发现，泰国肝内胆管癌的微卫星不稳定性（MSI）被归类为低频MSI，并且DNA MMR系统通过hMSH2和hMLH1基因突变，在其致癌过程中并未发挥主要作用。