大肠癌中端粒长度与DCC基因mRNA表达的研究

目的 分析端粒长度及DCC基因mRNA表达在大肠癌及腺瘤发生发展中的作用。方法 采用Sourthern印迹杂交及RT-PCR技术，分别检测46例大肠腺瘤及62例大肠癌组织中的端粒限制性片段（TRF）长度及DCCmRNA表达状态并观察它们与肿瘤临床病理的关系。结果 在大肠癌及大肠腺瘤中，TRF长度较正常组织明显缩短，其缩短者占53.2%和41.3%，而延长者仅占6.5%和4.4%，结肠癌的TRF长度也较直肠癌的TRF长度明显缩短，DCCmRNA表达缺失率在大肠癌及大肠腺瘤中则分别达62.9%和34.8%，显著高于正常组织（1.6%)；同时，大肠癌患者的平均TRF长度还随患者年龄的增长而缩短，DCCmRNA表达缺失率则随肿瘤的分化程度下降及临床阶段的进展而升高，但DCCmRNA表达缺失与TRF长度缩短在大肠癌中未表现出明显的相关性。结论 端粒缩短与DCCmRNA表达缺失与TRF长度缩短在大肠癌中未表现出明显的相关性。结论 端粒缩短与DCCmRNA表达缺失可能是大肠腺瘤恶变及大肠癌形成过程中较具特征表现的生物学异常行为。

Telomere length and DCC gene mRNA expression of human large intestine cancers

OBJECTIVE: To evaluate the role of telomere and DCC in tumor transformation and progression. METHODS: Telomere length and DCC gene mRNA expression were examined by southern blot hybridization and RT-PCR analysis in 46 adenomas of large intestine, 62 cancers of large intestine and corresponding normal mucosa. RESULTS: Shortening of the telomere was present in the tissues of 41.3% of the adenomas and 53.2% of the cancers, and their average TRF lengths were significantly shorter than those of corresponding normal mucosa(P<0.05, P<0.01), whereas the telomere elongation was only detected in 4.4% and 6.5% of the adenomas and cancers respectively. In addition, the average telomere length in colon carcinomas was also shorter than that in rectal carcinomas. Moreover, the average telomere lengths of the colorectal cancer mucosa became shorter with age. The rates of DCC mRNA expression deletion were 34.8% and 62.9% in the tissues of adenomas and cancers respectively. The DCC mRNA expression deletion occurred more frequently in poorly differentiated and Dukes C, D carcinomas than in well-differentiated and Dukes A, B carcinomas (P<0.05, P<0.01). However, no significant correlation was found between the length of telomere and the deletion of DCC mRNA expression in the cancers of large intestine. CONCLUSION: The telomere shortening and DCC mRNA deletion may represent the biologic behavior of transformation and development of the large intestine cancers.