基于数据库挖掘分析SLC12A8在乳腺癌组织中的表达及与细胞耐药的关系  

Analysis of SLC12A8 gene expression in breast cancer tissues and its effect on drug-resistance based on data-mining

作　　者：李琪 徐银莹 谢冰雪 袁媛 姚荧[1] LI Qi;XU Yinying;XIE Bingxue;YUAN Yuan;YAO Ying(Department of Pharmacy,Wuxi Maturity and Child Health Care Hospital,Jiangsu Wuxi 214000,China)

机构地区：[1]无锡市妇幼保健院药学部,江苏无锡214000

出　　处：《现代肿瘤医学》2021年第22期3938-3943,共6页Journal of Modern Oncology

基　　金：江苏省药学会-天晴(连云港)医院药学基金项目(编号:Q2019080);江苏省无锡市卫生健康委科研项目(编号:Q202028);江苏省无锡市卫计委“科教强卫工程”青年医学人才项目(编号:QNRC025)。

摘　　要：目的:探讨SLC12A8在乳腺癌组织中的表达及临床意义,并分析其在乳腺癌耐药细胞中的表达。方法:利用Oncomine数据库分析SLC12A8在乳腺癌组织中mRNA表达情况,利用HPA数据库分析SLC12A8在乳腺癌组织中蛋白表达情况,采用Kaplan-Meier法分析SLC12A8表达水平与乳腺癌患者总生存期、无复发生存期和无远处转移生存期的关系。利用GEO数据库分析乳腺癌耐药细胞中SLC12A8的表达,进一步利用cBioPortal数据库分析乳腺癌耐药细胞中与SLC12A8共表达基因。结果:与正常乳腺组织相比,乳腺癌组织中SLC12A8 mRNA具有高表达(P<0.0001)且其蛋白表达水平也较高。通过生存分析发现低表达SLC12A8基因的乳腺癌患者总生存期(OS)、无复发生存期(RFS)和无远处转移生存期(DMFS)明显长于高表达者,高表达患者的预后更差(P<0.01)。乳腺癌耐阿霉素细胞MCF7/ADR中SLC12A8 mRNA表达高于非耐药细胞MCF7(P<0.05),SLC12A8表达与MCF/ADR中表达降低的GREB1、PDZK1、GFRA1基因呈负相关,且这三个基因与乳腺癌耐药密切相关。结论:SLC12A8基因在乳腺癌组织中呈现高表达,其表达水平与乳腺癌患者预后呈负相关,该基因可能通过与GREB1、PDZK1、GFRA1相互作用参与乳腺癌耐药过程。Objective:To analyze the expression and its clinical significance of SLC12A8 gene in breast cancer and investigate the expression of SLC12A8 expression in multi-drug resistant breast cancer cells through mining the related microarray data from Oncomine.Methods:The information and mRNA and protein expression of SLC12A8 was collected respectively from the Oncomine and HPA database.To explore its clinical significance,Kaplan-Meier method was used to analyze the relationship between SLC12A8 and overall survival(OS),recurrence-free survival(RFS)and distant metastasis-free survival(DMFS)of breast cancer patients.The GEO database was used to analyze the expression of SLC12A8 in doxorubicin-resistant or sensitive breast cancer cells.Then cBioPortal and GEO database was used to analyze the related gene of SLC12A8 in doxorubicin-resistant breast cancer cells.Results:Comparing with normal tissues,the mRNA expression of SLC12A8 gene in breast cancer tissues was significantly higher(P<0.0001),and so it is with the protein expression of SLC12A8.Survival analysis showed that the OS,RFS and DMFS of breast cancer patients with low expression of SLC12A8 gene were significantly longer than those with high expression,and the prognosis of patients with high expression was worse(P<0.05).The SLC12A8 mRNA expression was higher in doxorubicin-resistant breast cancer cells(MCF7/ADR)than in non-resistant breast cancer cell MCF7(P<0.05),and its expression was negatively related to GREB1,PDZK1,GFRA1 which was reduced in MCF7/ADR compared to MCF7,and these three genes were proved to participated in drug resistance process of breast cancer.Conclusion:The expression of SLC12A8 was higher in the breast cancer tissues,and its expression level was negatively correlated with the prognosis of breast cancer patients.This gene may be related to multi-drug resistant of breast cancer cells by interacting with GREB1 or/and PDZK1 or/and GFRA1.

关 键 词：乳腺癌 SLC12A8 数据库分析 耐药 

分 类 号：R735.9[医药卫生—肿瘤]