The insulin-like growth factor binding protein-3 and its death receptor in pancreatic ductal adenocarcinoma poor prognosis

Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) and its newly discovered death receptor (IGFBP-3R) have been reported to involve in a wide variety of cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) has not been elucidated yet. Here, 478 pancreatic cancers were screened for primary PDAC tumors. The samples were evaluated using quantitative reverse-transcriptase polymerase chain reaction, western blotting, and immunohistochemistry staining. The results indicated that relative IGFBP-3 mRNA expression and its protein level were reduced stage dependently in the PDAC tumors (p < .001 and p < .05, respectively). The subcellular distribution of IGFBP-3 was mainly nuclear only in Stage 0 + 1 (about 150 compared to adjacent normal tissues p < .05). The value for IGFBP-3R messenger RNA (mRNA) and protein were also reduced in tumors in compared to adjacent normal pancreatic tissues (p < .05). The Kaplan-Meier analysis also showed that mRNA expression of IGFBP-3 and IGFBP-3R was positively associated with survival, (p = .001). In addition, there is a strong association between low expression of IGFBP-3 and tumor size (p = .032), the lymphatic invasion (p = .001), the TNM (tumor, node, metastasis) staging (p = .001), tumor differentiation (p = .001), and PNI status (p = .021). Down-regulation of IGFBP-3R was also correlated with the tumor size (p = .01), the lymphatic invasion (p = .012) TNM staging (p = .001), tumor differentiation (p = .021) and PNI status (p = .038). In conclusion, IGFBP-3 and its receptor were down-regulated and their expression was associated with poor prognosis of PDAC.