Li Yujing, Zeng Beilei, Li Yunhai, Zhang Chong, Ren Guosheng
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PeerJ. 2019 Aug 1;7:e7431. doi: 10.7717/peerj.7431. eCollection 2019.
Rho GTPase-activating protein 10 (ARHGAP10), which catalyzes the conversion of active Rho GTPase to the inactive form, is downregulated in some cancers. However, little is known about ARHGAP10 in breast cancer.
The transcriptional expression level of ARHGAP10 in breast cancer was analyzed with the data downloaded from The Cancer Genome Atlas (TCGA) and Oncomine, then verified by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in 30 pairs of breast cancer tissues and the corresponding adjacent normal tissues. ARHGAP10 protein expression was examined by immunohistochemistry (IHC) in 190 breast cancer and 30 corresponding adjacent normal breast tissue samples. The associations between ARHGAP10 expression and clinicopathological characteristics of patients were analyzed, and Kaplan-Meier Plotter was used to assess the relationship between ARHGAP10 and relapse-free survival (RFS). Different expression levels of ARHGAP10 in response to chemotherapy agents were determined by GEO2R online tool. The potential biological functions of ARHGAP10 were analyzed by Gene Set Enrichment Analysis (GSEA) using data downloaded from TCGA.
ARHGAP10 mRNA and protein expression was lower in breast cancer tissues than in adjacent normal tissues. Low expression of ARHGAP10 was associated with advanced clinical TNM (cTNM) stage ( = 0.001) and high Ki-67 index ( = 0.015). Low expression of ARHGAP10 indicated worse RFS ( = 0.0015) and a poor response to chemotherapy ( = 0.006). GSEA results showed that ARHGAP10 was involved in signaling pathways including protein export, nucleotide excision repair, base excision repair, focal adhesion, JAK-STAT pathway and the actin cytoskeleton.
Rho GTP酶激活蛋白10（ARHGAP10）可催化活性Rho GTP酶转化为无活性形式，在某些癌症中表达下调。然而，关于ARHGAP10在乳腺癌中的情况知之甚少。
利用从癌症基因组图谱（TCGA）和Oncomine下载的数据，分析ARHGAP10在乳腺癌中的转录表达水平，然后通过逆转录定量聚合酶链反应（RT-qPCR）在30对乳腺癌组织及相应的癌旁正常组织中进行验证。采用免疫组织化学（IHC）检测190例乳腺癌组织及30例相应的癌旁正常乳腺组织样本中ARHGAP10蛋白的表达。分析ARHGAP10表达与患者临床病理特征之间的关联，并使用Kaplan-Meier Plotter评估ARHGAP10与无复发生存期（RFS）之间的关系。通过GEO2R在线工具确定ARHGAP10在不同化疗药物作用下的表达水平差异。利用从TCGA下载的数据，通过基因集富集分析（GSEA）分析ARHGAP10的潜在生物学功能。
乳腺癌组织中ARHGAP10的mRNA和蛋白表达低于癌旁正常组织。ARHGAP10低表达与临床TNM（cTNM）晚期（P = 0.001）和高Ki-67指数（P = 0.015）相关。ARHGAP10低表达提示RFS较差（P = 0.0015）且对化疗反应不佳（P = 0.006）。GSEA结果显示，ARHGAP10参与了包括蛋白质输出、核苷酸切除修复、碱基切除修复、粘着斑、JAK-STAT通路和肌动蛋白细胞骨架等信号通路。
