High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma

Abstract

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells' proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients' survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma.

Liver- and Microbiome-derived Bile Acids Accumulate in Human Breast Tumors and Inhibit Growth and Improve Patient Survival

“…As a general finding, FXR signaling in these cell lines led to oncosuppressive effects (27,44,45). Consistent with these observations, high FXR expression in human breast tumors was associated with favorable patient survival in one analysis (46). These data further substantiate our findings that the tumor bile acid content associates with a less aggressive disease and improved patient survival in breast cancer.…”

“…S8). Other studies have shown FXR protein expression in these cell lines and tumors using Western blot analysis and IHC (27,(44)(45)(46). As a general finding, FXR signaling in these cell lines led to oncosuppressive effects (27,44,45).…”

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

“…188,189 High FXR associated with smaller tumor size, high proliferation rate, relapse-free survival, distant metastasis-free survival, and overall survival in BC patients. 190,191 Indeed, FXR is an independent prognostic factor for overall and disease-free patients' survival. 191 Potential mechanisms of action include FXR-mediated inhibition of leptin-induced oncogenic cancer-associated fibroblasts (CAFs) in multiple BC cell lines by increasing suppressor of the cytokine signaling 3 (SOCS3) expression downstream of FXR-implicating an obesity-specific susceptibility.…”

“…190,191 Indeed, FXR is an independent prognostic factor for overall and disease-free patients' survival. 191 Potential mechanisms of action include FXR-mediated inhibition of leptin-induced oncogenic cancer-associated fibroblasts (CAFs) in multiple BC cell lines by increasing suppressor of the cytokine signaling 3 (SOCS3) expression downstream of FXR-implicating an obesity-specific susceptibility. 188 SOCS3 is downregulated in BC.…”

Farnesoid X receptor (FXR) as a potential therapeutic target in nonalcoholic fatty liver disease and associated syndromes

“…Вариации уровня miR-194 в опу-холях одного происхождения коррелируют со стадией ракового заболевания, с чувствительностью опухолей к терапии и с прогнозом [38][39][40]. Поскольку снижение уровня miR-194 может быть ассоциировано с увеличе-нием экспрессии FXR, представленность данного рецеп-тора может быть полезным прогностическим признаком не только для НАЖБП и связанных с ней патологий пе-чени, но и для раковых заболеваний различного проис-хождения [41][42][43].…”