BRCA1/2基因低频变异通过影响P53和PAX-8的表达而促进卵巢癌的转移机制

Low frequency mutation of brca1/2 gene promotes the study of ovarian cancer metastasis mechanism by affecting the expression of P53 and pax-8

目的探讨BRCA1/2基因低频变异与卵巢癌间的潜在关系,并分析其是否通过影响P53和PAX-8的表达而促进卵巢癌的转移。方法共收集30例卵巢癌伴淋巴或血行转移患者以及无转移的卵巢癌患者30例进行BRCA1/2基于的测序筛查,获取BRCA1、BRCA2基因外显子的突变位点,并选择包括错义突变、移码突变在内的潜在有害突变位点,采用免疫组化法检测卵巢癌组织中P53和PAX-8的表达,分析BRCA1/2基因低频变异与P53和PAX-8表达的相关性。结果伴转移的卵巢癌患者中共检测到到11个突变位点,杂合移码致病性突变6例,无义致病性突变2例,突变率为26.67%,明显高于无转移的卵巢癌组织(P<0.05)。在伴转移组中,BRCA1/2基因低频变异患者中均存在P53和PAX-8的高表达,表达率为100%和87.5%,差异具有统计学意义(P<0.05),进一步Speramen等级相关分析显示,随着BRCA1/2低频变异率增加,PAX-8和P53的表达增强,两者间具有明显的正相关性(r=0.847和0.749,P<0.01)。结论BRCA1/2基因的位点突变可能通过影响P53和PAX-8的表达而介导卵巢癌的转移,BRCA1/2基因是影响卵巢癌恶性生物学行为进展的重要基因。

Objective To explore the potential relationship between low-frequency mutation of brca1/2 gene and ovarian cancer,and to analyze whether it promotes ovarian cancer metastasis by affecting the expression of P53 and pax-8.MethodsCollect 30 cases of ovarian cancer patients with lymphatic or blood bank transfer with and without transfer of 30 patients with ovarian cancer BRCA1/2 based on the sequencing of screening,access to BRCA1 and BRCA2 gene mutations of exon,and select,including missense mutation,frameshift mutations,potentially harmful mutations,using immunohistochemical method to detect ovarian cancer tissues the expression of P53 and PAX-8,analysis of BRCA1/2 gene frequency variation and correlation of P53 and PAX-8 expression.Results A total of 11 mutation sites were detected in ovarian cancer patients with metastasis,including 6 cases of heterozygous transcoding pathogenic mutation and 2 cases of nonsense pathogenic mutation,with a mutation rate of 26.67%,significantly higher than that in ovarian cancer tissues without metastasis(P<0.05).In the group with transfer,BRCA1/2 gene frequency variation in patients with high expression of P53 and PAX-8,expression rate was 100%and 87.5%,the difference statistically significant(P<0.05),and further Speramen rank correlation analysis showed that as BRCA1/2 low frequency variation rate increases,PAX-8 and the expression of P53,has obvious positive correlation between(r=0.847 and 0.749,P<0.01).Conclusion The mutation of brca1/2 gene may mediate ovarian cancer metastasis by affecting the expression of P53 and pax-8,and brca1/2 gene is an important gene affecting the progress of biological behavior of ovarian cancer.