J Cancer 2020; 11(10):3041-3051. doi:10.7150/jca.39645

Research Paper

Identification of Key Gene and Pathways for the Prediction of Peritoneal Metastasis of Gastric Cancer by Co-expression Analysis

Simeng Zhang1,2,3*, Dan Zang1,2,3*, Yu Cheng1,2,3, Zhi Li1,2,3, Bowen Yang2,3, Tianshu Guo1,2,3, Yunpeng Liu1,2,3, Xiujuan Qu1,2,3, Xiaofang Che1,2,3✉

1. Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China;
2. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China;
3. Liaoning Province Clinical Research Center for Cancer, Shenyang 110001, China
*These authors contributed equally to this study.

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Citation:
Zhang S, Zang D, Cheng Y, Li Z, Yang B, Guo T, Liu Y, Qu X, Che X. Identification of Key Gene and Pathways for the Prediction of Peritoneal Metastasis of Gastric Cancer by Co-expression Analysis. J Cancer 2020; 11(10):3041-3051. doi:10.7150/jca.39645. Available from http://www.jcancer.org/v11p3041.htm

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Abstract

Peritoneal metastasis is the most common pattern in advanced gastric cancer and can predict poor disease prognosis. Early detection of peritoneal tumor dissemination is restricted by small peritoneal deposits. Therefore, it is critical to identify a novel predictive marker and to explore the potential mechanism associated with this process. In the present study, one module that correlated with peritoneal metastasis was identified. Enrichment analysis indicated that the Focal adhesion and the PI3K-Akt signaling pathway were the most significant pathways. Following network and Molecular Complex Detection (MCODE) analysis, the hub-gene cluster that consisted of 19 genes was selected. Methionine sulfoxide reductase B3 (MSRB3) was identified as a seed gene. Survival analysis indicated that high expression levels of MSRB3 were independent predictors of peritoneal disease-free survival (pDFS) as determined by univariate (HR 8.559, 95% CI; 3.339-21.937; P<.001) and multivariate Cox analysis (HR 3.982, 95% CI; 1.509-10.509; P=.005). Furthermore, patients with high levels of MSRB3 exhibited a significantly lower Overall Survival (OS) (log-rank P = 0.007). The external validation was performed by the (The Cancer Genome Atlas (TCGA)) (log-rank P = 0.037) and Kaplan Meier-plotter (KMplotter) (log-rank P = 0.031) data. In vitro experiments confirmed that MSRB3 was a critical protein in regulating gastric cancer cell proliferation and migration. In conclusion, High expression levels of MSRB3 in GC can predict peritoneal metastasis and recurrence as well as poor prognosis. Furthermore, MSRB3 was involved in the regulation of the proliferation and migration of GC cells.

Keywords: gastric cancer, peritoneal metastasis, WGCNA, MSRB3, PI3K-Akt