ITIH4 is a novel serum biomarker for early gastric cancer diagnosis

Background: Gastric cancer (GC) is one of the most lethal forms of cancer due to the absence of tools for its early detection. Here, we explored critical biomarkers for early diagnosis. Materials and methods: Key biomarkers in serum from patients with early gastric cancer (EGC) and healthy controls (HCs) were identified via mass spectrometry and the expression of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) was evaluated using several methods. Furthermore, ITIH4 expression in sera and exosomes from patients with EGC, advanced GC (AGC), low grade intraepithelial neoplasia (LGN), chronic superficial gastritis with Helicobacter pylori infection (Hpi), other systemic malignant tumors (OSTs), and healthy controls was also evaluated. Results: ITIH4 was identified as a key biomarker in patients with EGC. Its expression level in serum from the EGC group, which showed the highest specificity (94.44%), was significantly higher than those in sera from other GC groups as well as the control. Western blot analysis, immunohistochemical staining, and exosome analysis also confirmed ITIH4 expression in sera from patients with GC, but not in those from healthy individual. Conclusion: ITIH4 is a key biomarker in serum from patients with EGC and has potential as a high value diagnostic marker for EGC.