Correlation between the expression of hypoxia-inducible factor-1α or histone deacetylase 1/metastasis-associated protein 1 complex and poor prognosis on human pancreatic carcinoma

Abstract

21012 Background: Hypoxia-inducible factor-1a (HIF-1a) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1a expression, however, the association between HIF-1a and histone deacetylase 1 (HDAC1) / metastasis-associated protein 1 (MTA1) is not fully understood. Here, we explored the involvement of HIF-1a and HDAC1/MTA1 in human pancreatic carcinoma. Methods: HIF-1a, HDAC1 and MTA1 expressions were detected by immunohistochemistry in surgical specimens obtained from 39 patients with pancreatic carcinoma. The correlations between the expression of HIF-1a, HDAC1 or MTA1 and clinical features, and the prognosis of patients with pancreatic carcinoma were then analyzed. Results: HIF-1a, HDAC1 and MTA1 positive stainings were found in 16 of 39 cases (41%), 22 of 39 cases (56%) and 12 of 39 cases (31%), respectively. There was no correlation between HIF-1a, HDAC1 or MTA1 expression levels and any of the clinical parameters examined. The five-year survival rate for pancreatic carcinoma patients with HIF-1a and HDAC1 positive stainings were significantly lower than for those patients with HIF-1a and HDAC1 negative stainings (P = 0.0243 and 0.0433). The MTA1 positive stainings group did not have a significantly worse prognosis than the MTA1 negative stainings group (P = 0.9694). In addition, the five-year survival rate for the HDAC1/MTA1 positive stainings group was statistically significantly worse than for the other groups (P = 0.0386). Conclusions: These results suggest that HIF-1a expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis on human pancreatic carcinoma, and indicate that HIF-1a and HDAC1/MTA1 is a promising therapeutic target in pancreatic carcinoma treatment. No significant financial relationships to disclose.