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Open Access Research article

Overexpression of SLC38A1 is associated with poorer prognosis in Chinese patients with gastric cancer

Jing Xie1*, Ping Li2, Hui-feng Gao1, Jian-xin Qian3, Ling-Yan Yuan3 and Jie-jun Wang3*

Author Affiliations

1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai 200032, China

2 Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China

3 Department of oncology, Changzheng Hospital, the Second Military Medical University, 64 HeTian Road, Shanghai 200003, China

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BMC Gastroenterology 2014, 14:70  doi:10.1186/1471-230X-14-70

Published: 9 April 2014

Abstract

Background

Current literature has demonstrated that host glutamine depletion facilitates tumorigenesis. Likewise, the glutamine transporter SLC38A1 is putatively associated with malignant transformation and tumor progression. Taken together, this forms the premise for undertaking the current study. The twofold aim of this study was to provide insight into whether or not a variance in the expression of SLC38A1 exists between human gastric cancer and healthy human tissues, and to determine how silencing the SLC38A1 gene could affect the proliferation, viability, migration, and invasion of gastric cancer cells.

Methods

Immunohistochemical staining was used to analyze the expression of SLC38A1 in gastric cancer tissues and adjacent healthy mucosa in 896 patients with pathologically confirmed gastric cancer who had underwent R0 resection. SH-10-TC cells (a gastric cancer cell line) were used to examine whether silencing SLC38A1 with siRNA could affect cell viability, migration and invasion.

Results

The SLC38A1 protein was very low or undetectable in healthy gastric mucosa. In contrast, strong staining of SLC38A1 protein was found in the cytoplasm in 495 out of the 896 gastric cancer samples. More pronounced SLC38A1 expression in gastric cancer tissues was significantly associated with age, differentiation status, lymph node metastasis, TNM stage and PCNA (proliferating cell nuclear antigen) expression. Upon univariate survival analysis, SLC38A1 expression was correlated with poor survival. Multivariate survival analysis revealed that SLC38A1 was an independent prognostic factor.

Conclusion

SLC38A1 is overexpressed in gastric cancer, which suggests that it is contributory to tumor progression. These results encourage the exploration of SLC38A1 as a target for intervention in gastric cancer.

Keywords:
Gastric cancer; Tissue microarray; Immunohistochemistry; SLC38A1; Prognostic factor