人结肠癌组织中肿瘤耐药相关基因的表达及其临床意义

Expression of Drug Resistance-associated Tumor Genes in Human Colonic Carcinoma Tissue and its Clinical Significance

人结肠癌对化疗药物的耐药是其化疗失败的主要原因,一些与肿瘤耐药相关的基因从中起着一定作用,有关耐药相关基因在人结肠癌中表达水平的联合检测报道较少。目的:探讨人结肠癌组织中耐药相关基因p21(WAF1/CIP1)、MRP2、BRCA2、CYP3A5、BCRP和ELK-1转录水平的表达及其临床意义。方法:对30例结肠癌手术标本的癌组织、癌旁组织和正常组织分别以逆转录聚合酶链反应(RT-PCR)法检测肿瘤耐药相关基因p21(WAF1/CIP1)、MRP2、BRCA2、CYP3A5、BCRP和ELK-1转录水平的表达,比较它们在不同组织中表达的差异及其与肿瘤临床特点之间的关系。结果:结肠癌组织中,MRP2转录表达水平显著高于正常组织(P=0.037);CYP3A5转录表达水平显著低于正常组织(P=0.042);ELK-1转录表达水平显著高于癌旁组织和正常组织(P=0.016和P=0.022)。在结肠癌组织和正常组织中,肿瘤耐药相关基因转录水平表达两两之间相关性有不同。结肠癌组织中,肿瘤耐药相关基因与结肠癌临床特点之间均无相关性。结论:在结肠癌的发生和耐药过程中,肿瘤耐药相关基因MRP2、CYP3A5和ELK-1起了一定作用,而p21(WAF1/CIP1)、BRCA2和BCRP基因的作用可能不明显。

Background： Drug resistance of human colonic careinoma is the main cause of its poor response to chemotherapy, which is partly due to some drug resistance-associated genes. The previous studies seldom paid attention to the combined determination of the expressions of drug resistance-associated genes in human colonic carcinoma. Aims： To appraise the expressions of drug resistance-associated genes, such as p21^（WAF1/CIP1）, MRP2, BRCA2, CYP3A5, BCRP and ELK-1 in human colonic carcinoma at the transcriptional level and their significance. Methods： Tissue specimens of cancerous, paracancerous and normal colonic tissues were obtained surgically from 30 patients with primary colonic carcinoma. The expressions of p21^（WAF1/CIP1）, MRP2, BRCA2, CYP3A5, BCRP and ELK-1 at the transcriptional level were, determined by using reverse transcriptase polymerase chain reaction （RT-PCR）. The discrepancies of their expressions at the transcriptional level in different tissue specimens and the relationship between the expressions of individual genes and clinical features of colonic carcinoma were analyzed by correlation analysis. Results： The expression of MRP2 at the transcriptional level was higher （P：0.037） and that of CYP3A5 was lower （P=0.042） in the cancerous tissue than those in the normal tissue. And that of ELK-1 was higher （P=0.016 and P=0.022） in cancerous tissue than those in the paracancerous and normal tissues. The relationships of the expressions at the transcriptional level of every two genes in all six genes tested were different in the cancerous tissues compared with that in the normal tissues. There were no close relationships between the expressions at the transcriptional level of all the above genes and the clinical features of human colonic cancer. Conclusions： MRP2, CYP3A5 and ELKI may play some roles in the occurrence and development of drug resistance of human colonic carcinoma. But the roles of p21^（WAF1/CIP1）, BRCA2, BCRP may not apparent during that process.