Upregulated Solute Carrier SLC39A1 Promotes Gastric Cancer Proliferation and Indicates Unfavorable Prognosis

Abstract

Backgrounds. Solute carrier 39A1 (SLC39A1) is an indirect zinc transporter which showed diverse tumor-related functions in different malignancies. Here, we aimed to investigate its expression and role in gastric adenocarcinoma. Methods. A retrospective gastric adenocarcinoma cohort (n = 154) was collected from our hospital to test their tissue expression of SLC39A1 through immunohistochemical staining method. After SLC39A1 overexpression or knockdown, proliferation and invasion assays were conducted for proliferation and invasion estimation, respectively. Xenograft in nude mice was used as the in vivo strategy to validate in vitro findings. Results. Compared with adjacent stomach tissues, gastric adenocarcinoma tissues showed significantly higher SLC39A1 on both mRNA and protein levels. Higher SLC39A1 was observed in patients with larger tumor size ( $P=0.003$ ) and advanced tumor stages ( $P<0.001$ ). Univariate ( $P=0.001$ ) and multivariate analyses ( $P=0.035$ ) confirmed the independent prognostic significance of SLC39A1 on gastric adenocarcinoma outcomes. The median survival time was 22.0 months in patients with high-SLC39A1 expression, while up to 57.0 months in those with low-SLC39A1 ( $P=0.001$ ). In vitro and in vivo assays demonstrated that overexpressing SLC39A1 could promote gastric cancer growth and invasion, while silencing SLC39A1 led to opposite effects. Conclusions. Aberrant high-SLC39A1 expression can serve as an independent unfavorable prognostic factor for gastric adenocarcinoma. High SLC39A1 is critical for a more aggressive tumor phenotype by promoting cell proliferation and invasion. Therefore, targeting SLC39A1 may provide novel therapeutic insights.