Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Abstract

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma

“…In a subgroup analysis of patients with and without lymph node metastases, there were no significant differences in Cx43 and NEDD9 expression in patients without lymph node metastases , but patients with lymph node metastases showed higher expression of epithelial NEDD9 (Table 1, Figure 2). (14,(16)(17)(18)(19). Similar as in our study, expression of NEDD9 was found significantly increased in the tissue of pancreatic ductal adenocarcinoma compared to adjacent pancreatic tissue (18), but the same was not established in colorectal cancer (19).…”

Clinical Significance of Serum NEDD9 Levels in Patients with Pancreatic Cancer

“…Pancreatic cancer (PC) is a highly lethal malignancy. Extensive research is being conducted to identify novel diagnostic, predictive, and prognostic biomarkers for PC [18]. NEDD9 supports oncogenic signaling in a number of solid and hematologic tumors.…”

“…Little is known about the role of NEDD9 in PC but available data suggest elevated NEDD9 levels have been found in PC patients and it can have a prognostic role [15,16,17,18,20]. High levels of expression of NEDD9 were significantly correlated with clinical staging, lymph node metastasis, and histological differentiation in PC patients [15].…”

“…High levels of expression of NEDD9 were significantly correlated with clinical staging, lymph node metastasis, and histological differentiation in PC patients [15]. NEDD9 expression was not statistically correlated with tumor stage and grade, gender, or patient survival in another study done by Radulović et al [18].…”

MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9 

“…Studies have observed that NEDD9 is up-regulated and may promote the invasion and metastasis of many types of human malignancy, including PAC. 12,13 We also demonstrate that the SRC/STAT3 pathway may be involved in the biological function of miR-1252-5p targeting of NEDD9 in PAC.…”