胃癌Kai-1基因缺失与突变的研究

Loss and mutation of Kai- 1 gene in gastric cancer

目的：探讨Kai-1基因的缺失与突变在胃癌演进与转移中的意义。方法：提取30例胃癌患者的肿瘤组织（16例无淋巴转移，14例有淋巴转移），30例癌旁正常组织的RNA，RT—PCR扩增，电泳检测，测序验证Kai-1基因的缺失情况；并提取发生缺失的肿瘤组织的DNA，PCR扩增，测序探讨Kai-1基因的突变情况。结果：30例组织标本中12例出现Kai-1基因exon9缺失（10例杂合缺失，2例纯合缺失），30例癌旁正常组织中有5例出现Kai-1基因exon9缺失（5例杂合缺失）；在胃癌组织中Kai-1基因缺失频率显著高于在癌旁正常组织（P〈0．05）；在有淋巴转移的胃癌组织中，缺失的频率明显高于无淋巴转移的胃癌组织（P〈0．05），在胃癌中晚期（Ⅲ-Ⅳ期）明显高于早期（I-Ⅱ期）（P〈0．05），而Kai-1基因的缺失频率与胃癌患者的年龄、性别、组织学类型以及分化程度无关（P〉0．05）。结论：Kai-1基因缺失与突变可能与胃癌演进、转移有关，检测其缺失或突变可作为判断胃癌的演进与转移的客观临床指标。

Objective：To explore the significance of loss and mutation of Kai - 1 gene in the progression and metastasis of gastric cancer（GC）. Methods： The deletion of Kai -1 gene was detected by using RT -PCR and validated by sequencing in the tumor of 30 cases of GC and 30 normal cases near the tissues of GC ;the mutation of the domain of exon9 was detected by using PCR and judged by sequencing in the tissues of GC with the deletion of exon9 in the Kai - 1 gene. Results：The deletion of exon9 in the Kai - 1 gene was found in 12 of 30 gastric cases （40%） and in 5 of 30 normal cases near the gastric tissues（ 16.7% ） ,the frequency of exon9 deletion was significantly higher in the gastric tumors than in normal cases （P 〈 0.05 ） ;The frequency of exon9 deletion was significantly higher in gastric tumors with lymphatic metastasis than that without lymphatic metastasis （P 〈 0.05 ）, and in advanced stage（Ⅲ - IV ） than in earlier stage（ I - II ） of the gastric cancer （P 〈0.05 ）. However,there was no significant difference of the frequency of exon9 deletion when stratefied by age, sex, histological type as well as differentiated degree of patients with GC （P 〉 0.05 ）. Conclusion：The deletion and mutation of Kai - 1 was associated with invasion and metastasis of GC and the detection of the deletion or mutation of Kai - 1 can be considered as an objective clinical marker to assess the progression and metastasis of GC.