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目的研究8号染色体上D8S277位点的杂合性缺失(LOH)和微卫星不稳定性(MSI)对内源性端粒酶抑制基因(PINX1)蛋白表达的影响,阐明PINX1基因遗传不稳定性与胃癌进展的关系。方法采用石蜡包埋组织抽提DNA,聚合酶链-单链构象多态性(PCR-SSCP)分析,常规银染检测D8S277位点的LOH和MSI,采用Envision免疫组织化学染色和Leica-Qwin计算机图像分析等方法。结果D8S277位点的LOH发生率在淋巴结转移组(21.15%)明显高于无淋巴结转移组(0,P<0.05);在胃癌TNMⅢ+Ⅳ期(24.39%)显著高于Ⅰ+Ⅱ期(3.33%,P<0.05)。PINX1蛋白阳性率在无淋巴结转移组(78.95%)明显高于有淋巴结转移组(48.08%,P<0.05);TNM分期Ⅰ+Ⅱ期(73.33%)明显高于Ⅲ+Ⅳ期(43.90%,P<0.05);蛋白表达阴性组LOH阳性率为32.28%,明显高于蛋白阳性组的2.50%(P<0.01)。结论PINX1基因的遗传不稳定性可能导致该抑癌基因突变,是肿瘤发生发展的一个因素,LOH和MSI通过不同的途径调控胃癌的发生和发展。
Objective To investigate the effect of heterozygosity deletion (LOH) and microsatellite instability (MSI) at D8S277 on chromosome 8 on the expression of endogenous telomerase inhibitor (PINX1), and to elucidate the genetic instability of PINX1 gene And the progress of gastric cancer. Methods DNA was extracted from paraffin-embedded tissue by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). LOH and MSI of D8S277 were detected by conventional silver staining. Envision immunohistochemical staining and Leica-Qwin computer Image analysis and other methods. Results The incidence of LOH in D8S277 was significantly higher in lymph node metastasis group (21.15%) than in non-lymph node metastasis group (0, P <0.05), significantly higher in gastric cancer TNMⅢ + Ⅳ stage (24.39% %, P <0.05). The positive rate of PINX1 protein in lymph node metastasis group (78.95%) was significantly higher than that in lymph node metastasis group (48.08%, P <0.05). The positive rate of PINX1 protein in stage Ⅰ + Ⅱ was significantly higher than that in stage Ⅲ + Ⅳ (43.90% P <0.05). The positive rate of LOH in the protein negative group was 32.28%, which was significantly higher than that in the protein positive group (2.50%, P <0.01). Conclusion The genetic instability of PINX1 gene may result in the mutation of tumor suppressor gene. It is a factor of tumor development. LOH and MSI regulate the occurrence and development of gastric cancer through different pathways.