基于数据库挖掘分析PDZK1与乳腺癌氟维司群耐药的相关性

Database mining-based analysis of the correlation between PDZK1 and fulvestrant resistance in breast cancer

目的 探讨在乳腺癌氟维司群耐药中发挥关键作用的基因。方法 通过GEO公共数据库筛选两组氟维司群耐药细胞数据集,获取与氟维司群耐药相关的基因,分析蛋白互作网络(PPI)蛋白互作网络,筛选关键耐药基因,结合TCGA数据库分析关键基因临床预后相关性,通过细胞模型验证其生物学功能。结果 GEO数据库分析发现PDZ结构域蛋白1(PDZK1)在氟维司群耐药株呈显著低表达(P<0.05)。TCGA数据库显示PKZK1高表达与肿瘤临床分期呈显著负相关,分析发现PDZK1表达与乳腺癌患者预后良好显著相关,在乳腺癌细胞模型中过表达PDZK1基因可以提升氟维司群治疗的敏感度。结论 PDZK1的表达与氟维司群治疗耐药呈负相关,雌激素受体阳性乳腺癌患者中PDZK1高表达人群选择氟维司群治疗的临床获益更大。

Objective Exploring genes that play a key role in fulvestrant-resistance in breast cancer.Methods Two groups of fluvestrant resistance cell data sets were screened through GEO public database,genes related to fluvestrant resistance were obtained,PPI protein interaction network was analyzed,key drug resistance genes were screened,clinical prognostic correlation of key genes was analyzed in combination with TCGA database,and their biological functions were verified by cell model.Results GEO database analysis found PDZK1 to be significantly under-expressed in fulvestrant.The TCGA database showed that the high expression of PDZK1 was significantly negatively correlated with the clinical stage,and the analysis showed that the expression of PDZK1 was significantly correlated with the good prognosis of breast cancer patients.Overexpression of PDZK1 protein in breast cancer cell models enhanced the sensitivity of fulvestrant treatment.Conclusion PDZK1 expression is negatively correlated with fulvestrant treatment resistance,and the clinical benefit of fulvestrant treatment is greater for the group of patients in estrogen receptor-positive breast cancer with high PDZK1 expression.