Identification and validation of critical genes with prognostic value in gastric cancer

Ningxin Dong; Xiaolong Ma; Jing Shen; Yunlu Zheng; Guiyuan Li; Shaoqiang Zheng; Xiaoyi Huang

doi:10.3389/fcell.2022.1072062

Identification and validation of critical genes with prognostic value in gastric cancer

Front Cell Dev Biol. 2022 Dec 14:10:1072062. doi: 10.3389/fcell.2022.1072062. eCollection 2022.

Authors

Ningxin Dong^{1

2}, Xiaolong Ma¹, Jing Shen², Yunlu Zheng², Guiyuan Li³, Shaoqiang Zheng¹, Xiaoyi Huang^{4

5

6}

Affiliations

¹ Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Information, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Department of Oncology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Department of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
⁶ Shanghai Municipal Key Clinical Speciality, Shanghai, China.

Abstract

Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality rates. Molecular targeted therapies, including those targeting human epidermal factor receptor 2 (HER2), have proven to be effective in clinical treatment. However, better identification and description of tumor-promoting genes in GC is still necessary for antitumor therapy. Methods: Gene expression and clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Last absolute shrinkage and selection operator (LASSO) Cox regression were applied to build a prognostic model, the Prognosis Score. Functional enrichment and single-sample gene set enrichment analysis (ssGSEA) were used to explore potential mechanisms. Western blotting, RNA interference, cell migration, and wound healing assays were used to detect the expression and function of myosin light chain 9 (MYL9) in GC. Results: A four-gene prognostic model was constructed and GC patients from TCGA and meta-GEO cohorts were stratified into high-prognosis score groups or low-prognosis score groups. GC patients in the high-prognosis score group had significantly poorer overall survival (OS) than those in the low-prognosis score groups. The GC prognostic model was formulated as PrognosisScore = (0.06 × expression of BGN) - (0.008 × expression of ATP4A) + (0.12 × expression of MYL9) - (0.01 × expression of ALDH3A1). The prognosis score was identified as an independent predictor of OS. High expression of MYL9, the highest weighted gene in the prognosis score, was correlated with worse clinical outcomes. Functional analysis revealed that MYL9 is mainly associated with the biological function of epithelial-mesenchymal transition (EMT). Knockdown of MYL9 expression inhibits migration of GC cells in vitro. Conclusion: We found that PrognosisScore is potential reliable prognostic marker and verified that MYL9 promotes the migration and metastasis of GC cells.

Keywords: MYL9; epithelial-mesenchymal transition; gastric cancer; metastasis; prognostic model.