ARHGEF6 downregulation as a key mediator of tumor cell apoptosis in breast cancer

Yang Zhang; Dandan Zhou; Xuting Shen; Qinqin Song; Liuyang Yang; Wenbo Li; Xinxin Zhao; Wenxiang Fang; Bian Liu; Chencen Xing; Jisong Liu; Haoshu Fang; Qilun Zhang

doi:10.3892/ol.2025.15268

ARHGEF6 downregulation as a key mediator of tumor cell apoptosis in breast cancer

Oncol Lett. 2025 Sep 12;30(5):522. doi: 10.3892/ol.2025.15268. eCollection 2025 Nov.

Authors

Yang Zhang¹, Dandan Zhou², Xuting Shen³, Qinqin Song⁴, Liuyang Yang¹, Wenbo Li¹, Xinxin Zhao⁵, Wenxiang Fang⁶, Bian Liu¹, Chencen Xing⁷, Jisong Liu⁴, Haoshu Fang³, Qilun Zhang^{1

8}

Affiliations

¹ Department of Central Laboratory, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, Anhui 233000, P.R. China.
² Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
³ Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
⁴ Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University, Bengbu, Anhui 233000, P.R. China.
⁵ Core Facility Center for Medical Sciences, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
⁶ Animal Experiment Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
⁷ Department of Medical Education, The Fifth People's Hospital of Bengbu, Bengbu, Anhui 233000, P.R. China.
⁸ Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

Abstract

The present study aimed to identify novel clinical biomarkers for breast cancer (BRCA) through bioinformatics analyses and cellular experiments, due to the ongoing need for improved diagnosis and prognosis in BRCA. The GSE21422 and The Cancer Genome Atlas-BRCA (TCGA-BRCA) datasets were utilized to identify differentially expressed genes (DEGs) in BRCA. Common DEGs were subjected to comprehensive analyses, including risk score modeling, expression profiling, receiver operating characteristic curve evaluation, survival analysis and the development of a prognostic nomogram, to pinpoint clinically significant genes. Cellular assays were subsequently performed to investigate the functional roles of these key genes in BRCA. Through bioinformatics analyses, 5 genes with diagnostic value were identified: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1), Rac/Cdc42 guanine nucleotide exchange factor 6 (ARHGEF6), enhancer of zeste 2 polycomb repressive complex 2 subunit, integrin α1 (ITGA1) and PIK3R1, as well as 3 genes with prognostic value: ALDH1A1, ARHGEF6 and ITGA1. Among them, ARHGEF6 was recognized as the key gene in BRCA. Overexpression of ARHGEF6 was shown to suppress cell proliferation, invasion and migration, while promoting apoptosis in BRCA. In conclusion, by bioinformatics analysis, new diagnostic and prognostic biomarkers for patients with BRCA have been identified and the key gene, ARHGEF6, is a suppressor gene in BRCA progression. These findings provide new directions for BRCA clinical application.

Keywords: Rac/Cdc42 guanine nucleotide exchange factor 6; biomarkers; breast cancer; diagnosis; prognosis.