Prognostic Value and Biological Functions of RNA Binding Proteins in Stomach Adenocarcinoma

Junqing Li; Wenjie Zhou; Jitao Wei; Xing Xiao; Tailai An; Wenhui Wu; Yulong He

doi:10.2147/OTT.S297973

Prognostic Value and Biological Functions of RNA Binding Proteins in Stomach Adenocarcinoma

Onco Targets Ther. 2021 Mar 4:14:1689-1705. doi: 10.2147/OTT.S297973. eCollection 2021.

Authors

Junqing Li^#^{1

2}, Wenjie Zhou^#^{1

2}, Jitao Wei³, Xing Xiao³, Tailai An¹, Wenhui Wu¹, Yulong He^{1

2}

Affiliations

¹ Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, People's Republic of China.
² Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
³ Scientific Research Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To investigate the prognostic value and biological function of RNA binding proteins (RBPs) in stomach adenocarcinoma (STAD).

Materials and methods: Datasets of the differentially expressed genes (DEGs) were downloaded from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which the differentially expressed RBPs were determined. Functions and prognostic values of these determined RBPs were systematically investigated by a series of methods in bioinformatics analysis. In addition, transwell assays were performed to explore the effect of PTBP1 in STAD cells.

Results: Three hundred and sixty-two differentially expressed RBPs were determined, with 331 up-regulated and 31 down-regulated. Seven RBPs (PTBP1, PPIH, SMAD5, MSI2, RBM15, MRPS17, and ADAT3) were identified to be prognosis-related and adopted to construct a prognostic model. Compared with low-risk patients in TCGA training cohort, TCGA testing cohort and GEO cohort, high-risk patients had poorer overall survival (OS). The area under the ROC curves of this prognostic model were 0.804, 0.644 and 0.581 for TCGA training cohort, TCGA testing cohort and GEO cohort, respectively, justifying itself as a good prognostic model with reliable predictive ability. Using the seven identified RBPs, we then constructed a nomogram to generate a clinical utility model. The regulatory networks and functions of the seven RBPs were then investigated, the results of which demonstrated that MRPS17 and PTBP1 reduced the number of infiltrated immune cells. In-vitro experiments showed that the downregulation of PTBP1 weakened the migration and invasion capability of AGS and HGC27 cells.

Conclusion: The seven-gene signature can be used as a reliable STAD prognostic biomarker, and these findings help us better understand the prognostic roles and functions of RBPs in STAD.

Keywords: RNA binding proteins; TCGA; infiltrated immune cells; prognostic model; stomach adenocarcinoma.

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81772579), the Guangdong Province Science and Technology Plan Projects (2014A020212693), “3&3” Project of The First Affiliated Hospital of Sun Yat-Sen University (Yulong He) and Sanming Project of Medical in Shenzhen (SZSM201911010).