Abstract
The prognosis for patients with advanced gastric cancer (GC) remains poor. The identification of biomarkers relevant to the recurrence and metastasis of GC is advantageous for stratifying patients and proposing novel molecular targets. In the present study the oncological roles of SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1), a mediator of B-cell function, were elucidated in GC. The expression and methylation status of SAMSN1 were investigated in a panel of 11 GC cell lines. Immunohistochemical staining was performed to determine the pattern of SAMSN1 protein expression in gastric tissues. The prognostic impact of SAMSN1 expression was determined by analyzing 175 pairs of surgically resected gastric tissues. A marked decrease in the level of SAMSN1 mRNA was detected in 8/11 GC cell lines as compared with that in a non-transformed intestinal epithelium cell line (FHs 74) without promoter methylation. The mean expression level of SAMSN1 mRNA was reduced in GC tissues compared with normal adjacent tissues, an observation that was independent of tumor differentiation. The pattern of SAMSN1 protein expression was significantly correlated with that of SAMSN1 mRNA. Low SAMSN1 mRNA expression was significantly associated with tumor size (>60 mm; P=0.026) and shorter overall survival times (P=0.004). Multivariate analysis identified low SAMSN1 mRNA expression as an independent prognostic factor for poor overall survival (hazard ratio, 1.80; 95% confidence interval, 1.07-3.05; P=0.025). The difference in survival between the low and high SAMSN1 expression groups was more marked in patients with stage II/III GC compared to those with stage IV GC. In patients with stage II/III GC who underwent curative surgery, low SAMSN1 expression was associated with reduced disease free survival times. The results of the present study indicate that downregulation of SAMSN1 transcription may affect the progression and recurrence of GC, and therefore may represent a novel biomarker of GC.