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A Multimodal Imaging Framework to Advance Phenotyping of Living Label-free Breast Cancer Cells
Published on: August 22, 2025
Downregulated expression of ARHGAP10 correlates with advanced stage and high Ki-67 index in breast cancer
Yujing Li1, Beilei Zeng1, Yunhai Li1
1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
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.
Methods:
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.
Results:
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 (p = 0.001) and high Ki-67 index (p = 0.015). Low expression of ARHGAP10 indicated worse RFS (p = 0.0015) and a poor response to chemotherapy (p = 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.
Insights
Rho GTPase-activating protein 10 (ARHGAP10) is downregulated in breast cancer, correlating with advanced stage and poor relapse-free survival. Low ARHGAP10 expression indicates a worse response to chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Rho GTPase-activating protein 10 (ARHGAP10) regulates Rho GTPase activity and is implicated in various cancers.
- Its role in breast cancer remains largely unexplored.
Purpose of the Study:
- To investigate the expression levels of ARHGAP10 in breast cancer.
- To analyze the association between ARHGAP10 expression and clinicopathological features, patient survival, and chemotherapy response.
Main Methods:
- Analysis of ARHGAP10 mRNA expression using TCGA and Oncomine data.
- Validation of ARHGAP10 mRNA and protein expression via RT-qPCR and immunohistochemistry in patient tissues.
- Correlation analysis with clinicopathological characteristics and survival outcomes (Kaplan-Meier Plotter).
- Assessment of chemotherapy response and pathway analysis (GSEA).
Main Results:
- ARHGAP10 mRNA and protein levels were significantly lower in breast cancer tissues compared to normal adjacent tissues.
- Low ARHGAP10 expression correlated with advanced clinical TNM stage and high Ki-67 index.
- Reduced ARHGAP10 expression was associated with worse relapse-free survival and poorer response to chemotherapy.
- GSEA identified ARHGAP10 involvement in pathways such as protein export, DNA repair, focal adhesion, JAK-STAT signaling, and actin cytoskeleton regulation.
Conclusions:
- ARHGAP10 is downregulated in breast cancer and serves as a potential biomarker for disease progression and treatment response.
- Its dysregulation impacts key cellular processes, highlighting its significance in breast cancer pathogenesis.
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