Abstract
BackgroundPrognostic factors aid in the stratification and treatment of cancer. This study evaluated the prognostic significance of human epidermal growth factor receptor (HER) family members (HER1–4) expression in patients with operable pancreatic cancer.MethodsThe expression of individual HER proteins in patient tissue specimens was detected by immunohistochemistry staining. Patient follow-up time was between 1.0 and 78.1 months.ResultsPositive expression of HER1, HER2, HER3 and HER4 was detected in 41.4, 60.0, 24.3 and 65.7% of cases, respectively. Kaplan–Meier analysis revealed that HER3 positive expression was associated with decreased median survival time (12.0 vs. 25.6 months for HER3 positive and negative groups, respectively; P = 0.013). Cox’s regression confirmed that positive HER3 expression was an independent predictor of poor survival (RR = 3.684, P = 0.001). In contrast, HER4 negative patients had a significantly decreased median survival time when compared with HER4 positive patients (11.4 vs. 25.6 months, respectively; P = 0.027). However, HER4 was not an independent predictor of survival. No significant association between HER1 or HER2 expression and survival was observed (P = 0.626 & P = 0.859, respectively).ConclusionsHER3 is an independent prognostic marker for patients with operable pancreatic cancer. HER4 may also be of potential prognostic value in this disease and deserves further attention.
Highlights
Prognostic factors aid in the stratification and treatment of cancer
HER3 expression in pancreatic cancer cells and the inhibitory effects of anti-HER3 antibody Given the significant association observed between HER3 expression and poor survival in patients with many solid tumors, we wished to determine whether this receptor was expressed in pancreatic cancer cells in vitro and, if so, to determine its role in cellular proliferation
High levels of pHER3 expression were confirmed in the AsPC-1 pancreatic cancer cell line by western blotting, anti-HER3 monoclonal antibody (3D4) and anti-HER2 monoclonal antibody significantly down-regulated the expression of pHER3, and two drug combination showed synergistic inhibitory effect (Fig. 1a)
Summary
Prognostic factors aid in the stratification and treatment of cancer. This study evaluated the prognostic significance of human epidermal growth factor receptor (HER) family members (HER1–4) expression in patients with operable pancreatic cancer. Pancreatic cancer is the fourth leading cause of cancerrelated death in the United States with a 5-year survival rate of only 5% [1]. The human epidermal growth factor receptor (HER) family belongs to the tyrosine kinase receptor superfamily. It includes four highly homologous members, HER1, HER2, HER3 and HER4. HER family proteins and their associated downstream signaling networks regulate cellular activities such as gene expression, mitosis, differentiation, proliferation, survival, migration, invasion, and apoptosis [4, 5]. The small molecule HER1 tyrosine kinase inhibitor gefitinib has been used in the
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