An <i>In Silico</i> Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients

Abstract

Breast cancer (BC) is the main cause of cancer-related deaths of the world's female population as well as, particularly the Brazilian women (1). The National Cancer Institute in Brazil (INCA) estimated 66,280 new BC cases in 2020, comprising 29.7% of all tumors with a stratified primary location; this estimate is much higher than that for the cancer of the colon and rectum (9.2% of all cases) and cervical cancer (7.4%) in women. BC tumors can be categorized into five main subtypes that have been widely discussed in the literature according to the PAM50 classification: Basal (B), Luminal A (LA), Luminal B (LB), human epidermal growth factor receptor-2+ (HER2+), and normal breast-like (N). Another important classification encompasses triple-negative (TN) and non-TN (nTN) breast tumors, which are identified based on the immunohistochemistry outcomes for the hormone estrogen receptor (ER) and progesterone receptor (PR), and by the amplification of the HER2 (2, 3). The lack of expression of these three important membrane receptors classify them as TN (4). Approximately 80% of all basal tumors can be classified as TN, with similar expression profiles between these two classes (5, 6).

Gene network analysis using SWIM reveals interplay between the transcription factor‐encoding genes HMGA1, FOXM1, and MYBL2 in triple‐negative breast cancer

“…Interestingly, the importance of FZD9 was in silico demonstrated in Ref. [56], where the authors performed a computational analysis on the same GEO dataset (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76275) and suggested FZD9 as potential prognostic biomarker and new therapeutic target in TNBC tumors, noting significant associations between the high expression of FZD9 with the clinical–pathological characteristics, such as worse survival and prognosis, in TNBC patients.…”

Non-Coding RNA and Frizzled Receptors in Cancer

“…Similar to Fzd6, Fzd9 miRNA regulation contrasts with the other Fzd proteins. Studies of Fzd9 function show it to be upregulated in triple-negative breast cancer, but it is also tumor-suppressive in NSCLC ( de Bastos et al, 2021 ) , ( Tennis et al, 2010 ). However, knowledge of miRNA regulation of Fzd9 is limited, with only one published study showing miR-31 indirectly inhibiting Fzd9 expression and supporting cancer-promoting signaling in NSCLC in vitro and in vivo ( Tennis et al, 2016 ).…”