Decreased ITIH5 expression is associated with poor prognosis in primary gastric cancer.

Abstract

Inter-α-trypsin inhibitors (ITIs) are a family of serine protease inhibitors that comprise one light chain and a variable set of heavy chains (ITI heavy chains, ITIHs). ITIH5 is a new member of the ITIH family that contains two domains conserved in all known ITIHs: vault protein IT and von Willebrand type A. Recent studies suggest that ITIH5 expression may be altered in certain types of cancer. This study aimed to investigate ITIH5 expression in clinical tumor specimens from gastric cancer patients and its prognostic value for gastric cancer. ITIH5 expression was detected in fresh gastric cancer tissues (T) and the matched adjacent non-tumor tissues (ANT) using real-time quantitative reverse transcription-PCR and Western blotting. ITIH5 expression was retrospectively detected in 331 paraffin-embedded, banked samples using immunohistochemical staining. ITIH5 mRNA and protein expression was significantly downregulated in gastric cancer tissues compared to the ANT. There was a significant association between ITIH5 expression and histological grade (P = 0.020), N classification (P = 0.047), and clinical stage (P = 0.011). Patients with low ITIH5 expression had shorter survival compared to those with high ITIH5 expression. Multivariate analysis showed that ITIH5 expression was an independent prognostic factor for overall survival of gastric cancer patients (P = 0.034). Our data suggest that ITIH5 could play an important role in gastric cancer and may serve as a valuable prognostic biomarker and potential molecular therapy target for gastric cancer.