ARHGAP15在乳腺癌中的表达及临床相关性分析

Expression and clinical correlation analysis of ARHGAP15 in breast cancer

目的:探究Rho-GTPase激活蛋白15(Rho-GTPase activating protein 15,ARHGAP15)在乳腺癌中的表达及临床意义。方法:利用TCGA数据库检测ARHGAP15在乳腺癌中的表达,采用Kaplan-Meier、Logistics回归分析和单因素/多因素COX回归分析检测ARHGAP15与临床预后相关性。同时收集我院61例乳腺癌患者病理切片,检测ARHGAP15在乳腺癌中的表达并分析其与临床相关性。体外实验检测ARHGAP15对MCF-7和MDA-MB-231细胞的增殖和凋亡的影响。结果:TCGA数据库中ARHGAP15与T、N、M分期、预后、病理分级和年龄相关。本研究临床样本显示,ARHGAP15在乳腺癌中低表达,且与肿瘤直径、TNM分期、淋巴结转移和分子分型相关。COX单因素分析结果显示,TNM分期Ⅲ期、分子类型为三阴性、肿瘤直径≥3 cm与ARHGAP15低表达是影响乳腺癌患者预后的危险因素;多因素分析结果显示:肿瘤直径≥3 cm与ARHGAP15低表达是影响乳腺癌预后的危险因素。CCK-8和克隆实验发现过表达ARHGAP15抑制乳腺癌细胞增殖。细胞凋亡实验发现,ARHGAP15过表达组凋亡率较高。结论:ARHGAP15基因影响乳腺癌细胞的增殖和凋亡,且ARHGAP15低表达与乳腺癌的不良预后结局相关。

Objective:To explore the expression and clinical significance of Rho-GTPase activating protein 15(ARHGAP15)in breast cancer.Methods:Exploring the expression of ARHGAP15 in breast cancer using the TCGA database.Kaplan-meier,Logistics regression analysis and univariate/multivariate COX regression analysis were used to detect the correlation between ARHGAP15 and clinical prognosis.The pathological sections of 61 breast cancer patients in our hospital were collected.Subsequently,immunohistochemistry was used to detect the expression of ARHGAP15 in breast cancer and its clinical correlation.The effects of ARHGAP15 over-expression on the proliferation and apoptosis of MCF-7 and MDA-MB-231 cells were detected in vitro.Results:The mRNA level of ARHGAP15 correlated with T stage,N stage,M stage,Prognosis of chemotherapy,pathological grade and age by TCGA database.The clinical samples showed that ARHGAP15 was down-regulated in breast cancer and was associated with larger tumor diameter,poorer TNM stage,lymph node metastasis,and molecular typing.The results of COX univariate analysis showed that TNM stage 3,triple negative molecular type,tumor diameter≥3 cm and low expression of ARHGAP15 were the risk factors affecting the prognosis of breast cancer patients;Multivariate analysis showed that tumor diameter≥3 cm and ARHGAP15 low expression level were risk factors affecting the prognosis of breast cancer.Over-expression of ARHGAP15 inhibits breast cancer cell proliferation by CCK-8 and cloning assays.Over-expression of ARHGAP15 promotes apoptosis in breast cancer cells.Conclusion:ARHGAP15 gene affects the proliferation and apoptosis of breast cancer cells,and the low expression of ARHGAP15 is associated with poor prognosis of breast cancer.