The initiation and progression of gastric cancer are associated with inappropriate immune responses caused by chronic inflammation of the gastric mucosa.
To identify immunoregulatory molecules involved in gastric cancer progression, transcriptome analysis was conducted using tissues from patients with metastatic gastric cancer. Gastric cancer cells lines and 200 pairs (cancerous and non-cancerous) of gastric tissues from patients with gastric cancer were analyzed for gene expression, amplification, DNA hypermethylation and functions of the candidate molecule.
The transcriptome analysis revealed that marginal zone B and B1 cell specific protein (MZB1) was expressed at significantly decreased levels in primary gastric cancer tissues when compared with the corresponding normal gastric mucosae. PCR array analysis exploring genes expressed cooperatively with MZB1 revealed that differential expression of MZB1 mRNA in gastric cancer cell lines correlated positively with the levels of the mRNAs encoding estrogen receptor 1 and desumoylating isopeptidase 1. Hypermethylation of the MZB1 promoter was frequent in cell lines with decreased levels of MZB1 mRNA. siRNA-mediated knockdown of MZB1 significantly increased proliferation, invasion and migration of gastric cancer cell lines. Low MZB1 expression was an independent prognostic factor for recurrence after curative gastrectomy and was associated significantly with increased haematogenous recurrence.
The immunoregulator MZB1 acts as a suppressor and serves as a predictor for recurrence after curative resection in gastric cancer.
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All authors have declared no conflicts of interest.