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J Cancer 2023; 14(2):262-274. doi:10.7150/jca.77402 This issue Cite

Research Paper

MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5

Anshu Li^1*, Yan Guo^2*, Zhijie Yin¹, Xinghua Liu^1✉, Gengchen Xie^1✉

1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
2. Department of Chronic Noncommunicable Diseases Control and Prevention, Wuhan Center for Disease Control and Prevention, Wuhan, Hubei, China.
^* Equal contribution and Co-first authors

✉ Corresponding authors: Gengchen Xie: Email: gengchen_xieedu.cn; Xinghua Liu: Email: liu_xinghuaedu.cn.

Abstract

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Transcription factors (TFs) are essential gene expression regulators, and play critical roles in cancer development. However, the biological actions and prognostic value of TFs in GC remain unclear. In this study, we identified a risk model based on a 14-TF signature to predict recurrence-free survival in patients with GC. We further analyzed the ability of 14-TF to predict recurrence-free survival time in GC and found that a higher expression level of metastasis-associated protein 2 (MTA2) was associated with shorter overall survival and disease-free survival time in GC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promotes GC growth and metastasis. Furthermore, we identified MTA2 binding to the promoter of minichromosome maintenance deficient 5 (MCM5), thereby promoting GC progression. Overall, these findings strongly support the prognostic potential of the 14-TFs signature and suggest that targeting MTA2 may be a promising strategy to treat GC.

Keywords: gastric cancer, GEO, TCGA, MTA2, MCM5

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