nm23-H1基因在喉癌中杂合性丢失和微卫星序列不稳定性分析及表达的研究

Loss of heterozygosity and microsatellite instability of nm23-H1 gene expressed in laryngeal carcinoma

目的 探讨nm2 3 H1基因在喉鳞状细胞癌中杂合性丢失 (LOH)及表达情况。方法 选择nm2 3 H1基因内部及附近 5个微卫星多态标记 ,对 72例喉癌标本进行杂合性丢失和微卫星序列不稳定性检测 ,同时以RT PCR方法分析 38例配对喉鳞状细胞癌标本中nm2 3 H1基因表达情况。结果 LOH涉及至少 1个位点的频率高达 76 .39% ,5个位点均有LOH ,以D17S16 6 5处频率最高 ,达 38.10 %。 3个位点出现MI ,最高为 12 .70 %。nm2 3 H1基因杂合性丢失及微卫星不稳定与淋巴结转移、临床分期和肿瘤分化无显著相关性 (P >0 .0 5 ) ,但D17S16 6 5位点高LOH频率与低分化相关 (P <0 .0 5 )。癌、癌旁及转移淋巴结中nm2 3 H1表达不同 ,但差异无统计学意义 ,表达水平与淋巴结转移无关 (P >0 .0 5 )。结论 nm2 3 H1基因可能在喉鳞癌发生中起作用 ,杂合性丢失可能是影响基因功能的主要机制。

Objective To investigate the loss of heterozygosity (LOH) and the expression of nm23-H1 gene in laryngeal carcinoma. Methods LOH and microsatellite instability(MI) of nm23-H1 were studied in 72 samples of laryngeal carcinoma by using 5 microsatellite polymorphism markers in or around the gene, meanwhile the expression was compared among the normal, tumor and occurred corresponding metastatic lymphnode in 38 samples. Results LOH appeared at all the five loci, the highest frequency of 38.10% occurred at the D17S1665 polymorphism locus, LOH concerning at least one polymorphism locus reached 76.39%. 3 loci had MI with the highest frequency of 12.70%, and the total MI concerning at least one locus was 22.22%. No correlation was found between lymphnode metastasis, clinical stage and cancer cell differentiation with LOH or MI of nm23-H1 gene, P >0.05, but LOH at locus D17S1665 correlated with the differentiation of the tumor, P <0.05. The difference among tumor adjacent, normal tissue and metastatic lymphnode was not significant, no correlation between mRNA level of nm23-H1 gene and metastasis was found, P >0.05. Conclusion nm23-H1 gene may have important function in the oncogenesis of laryngeal carcinoma, LOH is the main dysfunction mechanism of nm23-H1 gene.