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FKBP10 Acts as a New Biomarker for Prognosis and Lymph Node Metastasis of Gastric Cancer by Bioinformatics Analysis and in Vitro Experiments

Authors Gong LB, Zhang C, Yu RX, Li C, Fan YB, Liu YP, Qu XJ

Received 9 March 2020

Accepted for publication 19 June 2020

Published 28 July 2020 Volume 2020:13 Pages 7399—7409

DOI https://doi.org/10.2147/OTT.S253154

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Leo Jen-Liang Su


Li-Bao Gong,1,2,* Chuang Zhang,1,2,* Ruo-Xi Yu,1,2 Ce Li,1,2 Yi-Bo Fan,1,2 Yun-Peng Liu,1,2 Xiu-Juan Qu1,2

1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiu-Juan Qu
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China
Tel +86-24-83282312
Fax +86-24-83282543
Email xiujuanqu@yahoo.com

Purpose: To explore the role of FKBP prolyl isomerase 10 (FKBP10) protein in the progression of gastric cancer.
Methods: Four independent gastric cancer databases (GSE27342, GSE29272, GSE54129 and TCGA-STAD) were used to identify differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify the abnormally active pathways in patients with gastric cancer. Univariate Cox regression analysis was used to identify genes with stable prognostic value in gastric cancer patients based on three independent gastric cancer databases (GSE15459, GSE62254, TCGA-STAD). Gene set enrichment analysis (GSEA) was used to explore the possible pathways related to FKBP10. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of FKBP10 mRNA in the HGC-27 and MKN-7 cell lines. Adhesion assay was used to detect changes in cell adhesion ability. FKBP10, ITGA1, ITGA2, ITGA5, ITGAV, ITGA6, P-AKT473, P-AKT308, AKT, and β-actin were evaluated by Western blot (WB).
Results: We first performed differential expression genes (DEGs) screening of four independent GC databases (GSE27342, GSE29272, GSE54129 and TCGA-STAD). Eighty-nine genes showed consistent up-regulation in GC, the results of pathway analysis showed that they were related to “Focal adhesion”. The prognostic value of these 89 genes was tested in three independent GC databases GSE15459, GSE62254 and TCGA-STAD cohort. Finally, 12 genes, in which the expression of FKBP10 was prominently increased in patients with lymph node metastasis (LNM), showed stable prognostic value. The following gene set enrichment analysis (GSEA) also showed that FKBP10 is mainly involved in cell adhesion process, while adhesion experiments confirmed that cell adhesion was down-regulated after silencing FKBP10 in GC cells, and adhesion-related molecules integrin αV and α 6 were down-regulated.
Conclusion: FKBP10 may be used as a marker for lymph node metastasis of GC and could be used as a potential target for future treatment of GC.

Keywords: FKBP10, GC, adhesion, lymph node metastasis, integrin

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