SETD2 indicates favourable prognosis in gastric cancer and suppresses cancer cell proliferation, migration, and invasion

Highlights: • SETD2 expression was decreased in gastric cancer. • Low-level expression of SETD2 in patients was significantly correlated with poor prognosis. • Overexpression of SETD2 inhibited proliferation, migration, and invasion significantly in GC cell lines. SET domain containing protein 2 (SETD2, also known as HYPB) is a 230-kD protein which is located at cytogenetic band p21.31 of chromosome 3. SETD2 is usually transformed or eradicated in multiple forms of tumours in humans. However, its primary function in gastric cancer (GC) remains unclear. In the current study, we investigated the mRNA and protein expression levels of SETD2 using immunohistochemistry, qPCR, RT-PCR, and immunoblotting. The function of SETD2 in GC cells was investigated by MTT and transwell assays. Our results revealed remarkably lower levels of SETD2 mRNA and protein in the tumour samples than in tumour-adjacent tissues. Decreased expression of SETD2 mRNA was observed in 122 (79.7%) of 153 primary tumour tissue samples. On the basis of the overall survival analysis, we could interpret that a low expression of SETD2 was correlated with a poor prognosis (P < 0.001, log-rank test). Multivariate survival analysis indicated that SETD2 was an obvious prognostic factor in patients with GC. SETD2 overexpression in GC cell lines significantly inhibited cell proliferation, migration, and invasion. Altogether, the investigation demonstrated the clinical significance of SETD2 expression, supporting the fundamental principle that a decrease in its level is an unfavourable event in the progression and prognosis of GC. Therefore, down-regulated SETD2 can presumably be a potential negative prognostic and progression marker for GC.