Overexpression of B2M and loss of ALK7 expression are associated with invasion, metastasis, and poor-prognosis of the pancreatic ductal adenocarcinoma.

Abstract

Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available markers have not yet been identified. In this study, we investigated the expression of B2M and ALK7 in 106 PDACs compared to precursor lesions of the pancreas. Immunohistochemistry was used to detect B2M and ALK7 protein expression. Positive B2M expression was significantly higher, while positive expression of ALK7 was significantly lower in PDAC than in precursor lesions (p < 0.01 or p < 0.001). Positive B2M expression was also significantly higher, while positive ALK7 expression was significantly lower in cases with well-differentiated adenocarcinoma, small tumor mass, no-metastasis of the lymph node, no-invasion of regional tissues, and TNM I or II stage disease than in cases having poorly-differentiated adenocarcinoma, large tumor mass, with metastasis and invasion, and TNM stage III or IV stage disease (p < 0.01). Univariate Kaplan-Meier analysis showed that B2M overexpression (p < 0.001), but lack of ALK7 expression (p < 0.001) was significantly associated with shorter overall survival. Cox multivariate analysis showed that differentiation, tumor mass, lymph node metastasis, invasion, TNM stage, and B2M levels negatively correlated with overall survival. In contrast, ALK7 level positively correlated with overall survival. Positive B2M and negative ALK7 expression are poor prognostic factors in PDAC patients. B2M and ALK7 might be important biological markers involved in the carcinogenesis, metastasis, invasion, and prognosis of PDAC.