Abstract
Bile acids (BAs) was critical in the initiation and progression of various tumors. However, their prognostic significance in pancreatic cancer was still illusive. In the present study, the expression and biological significance of FXR, a major receptor of BAs, in the lethal disease were evaluated in mRNA and protein levels. We found that FXR protein was elevated in the cancerous tissues, which was significantly higher than the adjacent tissues (p < 0.05). Meanwhile, our data showed that FXR was positively correlated with primary tumor location (p = 0.04) and poor survival (p = 0.002). Finally, COX regression model indicated that FXR protein was an independent prognostic factor (p = 0.01; HR = 2.15; 95% CI 1.27-3.63). Consistently, we also found a significant difference of FXR expression between the high and low groups in mRNA level (p < 0.001), and that high FXR expression confers a poor prognosis (p < 0.001). More importantly, the correlation assay showed that FXR was positively correlated Sp1 in both protein (r = 0.351, p = 0.008) and mRNA levels (r = 0.263, p < 0.01), with the simultaneously high expression indicated the worst prognosis on protein (p < 0.001) and mRNA levels (p < 0.001). Additionally, we also showed that FXR was elevated in the pancreatic cancer cells responsible for proliferation and migration. Overall, the data suggested co-high expression of the two factors was an independent prognostic factor (p < 0.001; HR = 3.27; 95% CI 1.86–5.76). Based on these data, we proposed a model to link FXR to Sp1, which included triggered FXR, p38/MAPK and/or PI3K/AKT signaling and phosphorylated Sp1, to illustrate the potential crosstalk between the two factors.
Highlights
Pancreatic cancer is a lethal disease with the 5-year survival rate of less than 5% and the median survival of 6 months, rendering it the fourth cause of cancerrelated deaths [1]
To investigate the role of Farnesoid X receptor (FXR) in pancreatic cancer; we initially examined its expression in mRNA level in clinical samples of pancreatic cancer
We examined their correlationship and found that they were positively correlated (p < 0.01, r = 0.263, Figure 1C) in mRNA levels with their simultaneously high expression indicated the poorest prognosis for the patients (p < 0.001, Figure 1D, 1E)
Summary
Pancreatic cancer is a lethal disease with the 5-year survival rate of less than 5% and the median survival of 6 months, rendering it the fourth cause of cancerrelated deaths [1]. Prior studies indicated that inactivation of FXR in cancer of liver and breast corresponded with increased propagation and decreased apoptosis [8, 9]. The existing studies had concluded an overexpression profile of FXR with conflicting roles. Lee JY showed that FXR functions as oncogene since it positively correlated with lymph node metastasis, migration and invasion of pancreatic cancer [11]; while another direct evidence, obtained more recently, indicated that elevated FXR in pancreatic cancer was responsible for a less aggressiveness phenotype and favors a better prognosis [12]. The conflicting results promoted us to re-evaluate the function of FXR in the lethal disease
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