应用变性高效液相色谱技术研究肿瘤转移抑制基因KAI1/CD82多态与结直肠癌发病及转移的相关性

Polymorphism of metastasis suppressor gene KAI1/CD82 detected using denaturing high-performance liquid chromatography techniques and its correlation with occurrence and metastasis of colorectal cancer

目的 研究肿瘤转移抑制基因KAII/CD82第8内含子IVS（8）6C11A/6T11G多态与结直肠癌发病及转移的相关性.方法 提取135例健康人、115例结直肠癌患者的外周血DNA,收集其相应的临床及病理资料,应用变性高效液相色谱技术,采用病例对照分组研究统计分析KAI1基因第8内含子剪接区域多态与结直肠癌发病及转移的相关性.结果 KAI1/CD82基因IVS（8）6T11G突变基因型检出率在正常人群为30.9%（84/135）,结直肠癌患者中为31.3%（72/155）,两者的差异无统计学意义（P=0.963）;在结直肠癌低龄（＜50岁）和高龄（≥50岁）患者之间以及性别之间差异均无统计学意义（均P＞0.05）;在常见的病理类型管状/管状乳头状腺癌、黏液腺癌中差异亦无统计学意义（P=0.633）;在病理分级中有一定的差异性,但无统计学意义（P=0.267）,而在有无淋巴结转移之间,两者差异有统计学意义（P.0.032）[6C11A有转移62.5%（80/128）,无转移76.5%（78/102）;6T11G有转移37.5%（48/128）,无转移23.5%（24/102）].结论 肿瘤转移抑制基因KAI1/CD82第8内含子剪接区域多态与结直肠癌的发病、病理类型无关,但可能影响肿瘤的淋巴结转移,提示KAI1/CD82基因IVS（8）6C11A/6T11G多态筛查可能成为结直肠癌患者预后风险评估的指标.

Objective To investigate the correlation of polymorphism of intron 8 （IVS-8） 6C11A /6T11G of metastasis suppressor gene KAI1/CD82 with the occurrence and metastasis of colorectal cancer.Methods From 135 healthy individuals and 115 patients with colorectal cancer, genomic DNA was extracted from peripheral blood, and their clinical data and pathological findings were retrieved.Correlation of the polymorphism at gene splicing region of the KAI1 IVS-8 with the occurrence and metastasis of colorectal cancer was analyzed in a case-control study by denaturing high-performance liquid chromatography （DHPLC） analysis.Results Mutant allelotype 6T11G of KAI1/CD82 gene IVS-8 was detected in 30.9% of healthy individuals （84/135） and 31.3% of colorectal cancer patients （72/155） , with no significant difference between the two groups （P=0.963）.The genotypes did not differ between younger （＜50 years） and older patients （=50 years） （P〉0.05）, between male and female（P〉0.05）, or among common pathological types including tubular or tubulopapillary adenocarcinoma and mucinous adenocarcinoma （P=0.633）.The prevalence of genotypes differed among pathological stages, but without statistical significance （P=0.267）.However, a statistical difference was shown between patients with and without lymph node invasion [6C11A detected in 62.5% vs 76.5% of patients with （80/128） and without metastases （78/102）; 6T11G detected in 37.5% vs 23.5% of patients with （48/128） and without metastases （24/102） ; （P=0.032） ].Conclusion The genetic polymorphism of IVS-8 in KAI1/CD82 gene may not be related with occurrence, pathological types of colorectal cancer but may play a role in lymph node metastasis, implicating that screening of 6C11A /6T11G polymorphism can be used to identify the prognosis of colorectal cancer patients.