Expression of sushi domain containing two reflects the malignant potential of gastric cancer

Hepatic recurrence of gastric cancer (GC) is uncontrollable. Discovery of causative oncogenes and the development of sensitive biomarkers to predict hepatic recurrence are required to improve patients' outcomes. In this study, recurrence pattern-specific transcriptome analysis of 57 749 genes was conducted to identify mRNAs specifically associated with hepatic metastasis of patients with stage III GC who underwent curative resection. GC cell lines were subjected to mRNA expression analysis, PCR array analysis, and siRNA-mediated knockdown. The expression levels of primary cancer tissues from 154 patients with resectable GC were determined and correlated with clinicopathological variables. Among 21 genes significantly overexpressed specifically in patients with hepatic recurrence, Sushi domain containing 2 (SUSD2) was selected as a promising target. PCR array analysis revealed that SUSD2 mRNA levels positively correlated with those of FZD7, CDH2, TGFR1, SPARC, ITGA5, and ZEB1. Functional analysis revealed that knockdown of SUSD2 significantly reduced the proliferation, migration, and invasiveness GC cell lines. Patients with high SUSD2 expression were more likely to experience shorter disease-free and overall survival. Analysis of the relation between disease recurrence pattern and SUSD2 levels revealed that significantly more patients with hepatic metastases expressed higher levels of SUSD2 mRNA. The cumulative incidence of hepatic recurrence was greater in patients with high SUSD2 expression. In conclusion, SUSD2 likely contributes to the malignant potential of GC and may serve as a novel biomarker that predicts hepatic recurrence after curative resection.