FOXQ1 is differentially expressed across breast cancer subtypes and potentially can serve as a prognostic marker
Authors: Elian Fahed A , Are Ubah , Nuin Paulo , Footz Tim , Brindley David N , McMullen Todd PW , Walter Michael A 
Published: April 2020

As a member of the forkhead box (FOX) superfamily of transcription factors, FOXQ1 plays a critical role in a wide range of biological processes, including angiogenesis, epithelial differentiation and smooth muscle differentiation. Emerging evidence also show FOXQ1 to play important roles in the development and progression of various cancers such as ovarian, pancreatic, and colorectal cancer. Particularly, FOXQ1 has been linked to facilitating tumor invasion and metastasis in breast cancer and has also been specifically associated with Triple Negative Basal‐like Breast Cancer (TN/BL BC). Furthermore, experimental studies have demonstrated FOXQ1 overexpression to promote/mediate epithelial to mesenchymal transition, invasion, stemness traits, and chemoresistance in breast cancer. These processes contribute substantially to poor prognosis in breast cancer patients, thus making FOXQ1 a potential target for the diagnosis and treatment of breast cancer tumors. In this study, we investigated the mechanisms leading to increased expression levels of FOXQ1 in BC through analysis of FOXQ1 copy number variation (CNV) and mRNA levels across BC patient subtypes and cell lines. Additionally, we assessed the prognostic significance of FOXQ1 in BC patients. Finally, K‐means clustering was conducted by using Python coding to identify unique clusters for FOXQ1 mRNA levels and CNV in BC cell lines.

We report for the first time, that FOXQ1 mRNA is differentially expressed across BC patients. FOXQ1 mRNA is significantly down regulated in Luminal (ER+) BC patients (n=6) when compared to control samples (n=6). FOXQ1mRNA expression is significantly up regulated in TN/BL BC patients (n=6) compared to Her2 (n=6) and ER+ BC (n=6) respectively. We also found FOXQ1 significantly has more copies in TN/BL BC compared to control samples. K‐means clustering analysis was conducted on BC cell lines, with the purpose of identifying distinct subpopulations based on FOXQ1 mRNA expression and CNV. Our supervised and unsupervised clustering analyses identified 3 and 4 clusters, respectively, among BC cell lines for FOXQ1 mRNA compared to their CNV. However, we found FOXQ1 mRNA expression to be independent of its CNV. Moreover, FOXQ1 mRNA was found to be highly expressed in numerous TN/BL cell lines. Lastly and most importantly, by applying the bioinformatic online tool GEPIA, Kaplan‐Meier survival curve analysis identified two risk groups with high (n=524) and low (n=531) FOXQ1 mRNA expression levels. Our Kaplan‐Meier survival analysis also showed patients with low FOXQ1 mRNA expression to have shorter overall survival time than those with high FOXQ1 mRNA expression (HR=0.71, P=0.042). In accordance to these results, we propose that FOXQ1 can serve as an emerging new prognostic biomarker for BC. Understanding the mechanism(s) underlying FOXQ1’s activation in breast cancer could facilitate the development of improved therapies for BC patients.

Support or Funding Information

Women and Children Health Research Institute Faculty of Medicine and Dentistry, U of A