Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma - Two Promising Breast Cancer Biomarkers

Sep 24, 2026

Invasive ductal carcinoma (IDC) remains a leading cause of breast cancer mortality due to high malignancy, metastasis, recurrence, and death rates. This study evaluates the expression of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) and 51 IDC tumors versus matched normal tissues using qPCR. TCGA shows elevated expression across cancers, with gene correlations in TCGA-BRCA, and methylation inversely associated with overexpression. Expression is upregulated in tumor samples, with ARHGAP11A linked to breastfeeding status and menstrual/menarche timing, and ARHGAP11B elevated in HER2-positive tumors. Results support protooncogenic roles and propose these genes as novel diagnostic and prognostic biomarkers for IDC.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Breast cancer epidemiology and risk factors

Molecular subtypes and receptor-based classification

Histological classifications and IDC characteristics

Rho family GTPases and RhoGAP relevance in invasion

Hindawi BioMed Research International Volume 2023, Article ID 8236853, 17 pages [https://doi.org/10.1155/2023/8236853](https://doi.org/10.1155/2023/8236853) Research Article Protooncogenic Role ofARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers Y. Naeimzadeh , 1 S. Ilbeigi ,2 H. Dastsooz ,3,4,5 M. Rafiee Monjezi ,6 Y. Mansoori ,7 and S. M. B. Tabei 8 1School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran 2 Walther-Straub Institute, Ludwig-Maximilians-Universität München, Munich, Germany 3Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy 4Candiolo, C/o IRCCS, IIGM-Italian Institute for Genomic Medicine, Turin, Italy 5Candiolo Cancer (IT), FPO-IRCCS, Candiolo Cancer Institute, Turin, Italy 6Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany 7Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran 8Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Correspondence should be addressed to S. M. B. Tabei; [tabeismb@sums.ac.ir](tabeismb@sums.ac.ir) Received 12 April 2023; Revised 22 June 2023; Accepted 31 October 2023; Published 23 November 2023 Academic Editor: Yuan Li Copyright © 2023 Y. Naeimzadeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully deﬁned. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR) . Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their signiﬁcant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDCpathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC. 1. Introduction Breast cancer (BC) is one of the most common cancer-related deaths among women worldwide [1–4], with approximately 2.3 million new cancer cases and 685,000 deaths reported in 2020 [5]. Generally, the etiology of BC is multifactorial, involving genetic, lifestyle, and environmental factors as well as reproductive behaviors. Several epidemiological studies have shown reproductive factors such as regular menstrual cycles, no history of breastfeeding, early age at menarche, contraceptive use, nulliparity, and ﬁrst full-term gestation can increase the risk of BCs [5–9]. Based on the expression level of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2 or ErbB2) g

FAQs

What is the main focus of the study?

The study investigates the protooncogenic role of ARHGAP11A and ARHGAP11B in invasive ductal carcinoma and assesses them as potential breast cancer biomarkers.

How were ARHGAP11A and ARHGAP11B expression levels measured?

Expression levels were analyzed using data from TCGA and by qPCR in 51 IDC tumor samples compared with matched normal tissues.

What relationship was observed between methylation and gene overexpression?

Promoter methylation of ARHGAP11A and ARHGAP11B showed a negative correlation with their overexpression.

How do the genes relate to clinical features such as breastfeeding and tumor subtype?

ARHGAP11A expression was lower in women who were breastfeeding and showed overexpression in cases with regular menstrual cycles and early menarche; ARHGAP11B was higher in HER2-positive tumors compared with HER2-positive and ER-positive categories described in the text.

Sep 24, 2026

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