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-AKT ₄₇₃, P-AKT ₃₀₈, 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