Comprehensive evaluation of FKBP10 expression and its prognostic potential in gastric cancer

Abstract

FK506 binding protein 10 (FKBP10) has been reported to be dysregulated in numerous types of cancer; however, few reports have investigated FKBP10 in gastric cancer (GC). The aim of the present study was to investigate FKBP10 expression in GC and to analyze its association with the prognosis of patients with GC. FKBP10 mRNA expression was evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The standardized mean differences of the meta-analysis were comprehensively evaluated for FKBP10 expression from a series of GEO datasets. Kaplan-Meier survival and Cox regression analyses were applied to predict the prognostic value of FKBP10 in patients with GC. Additionally, the protein expression levels of FKBP10 were validated by immunohistochemistry (IHC) in 40 GC and adjacent tissues. FKBP10 co-expression network and bioinformatics analyses were then used to explore the potential functional mechanisms of FKBP10. The results revealed that the mRNA expression levels of FKBP10 were significantly increased in GC within the TCGA and GEO databases. Survival analysis revealed that high FKBP10 expression results in poorer overall survival and disease-free survival (P<0.05). Multivariate cox regression analysis indicate FKBP10 as a dependent prognostic factor. The results of IHC indicated that the protein expression levels of FKBP10 were higher in GC tissues than in adjacent non-GC tissues (P<0.001). Co-expression networks and functional enrichment analysis suggested that FKBP10 may be involved in the development of GC via cell adhesion molecules and extracellular matrix-receptor interaction pathways. Therefore, the findings of the present study indicated that FKBP10 is upregulated in GC tissues, and suggests its potential prognostic value. Therefore FKBP10 may be a potential therapeutic target for the treatment of GC.

FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis

“…Olesen et al found that FKBP10 was overexpressed not only in colorectal cancer (CRC) but also in precancerous lesions consisting of hyperplastic polyps, benign tubular adenomas, or tubulo-villous adenomas from the same patients, suggesting a possible involvement of FKBP10 in CRC genesis [ 21 ]. FKBP10 was also found to be upregulated in KRAS-mutant lung adenocarcinoma, renal cell carcinoma, and gastric cancer, and knockdown of FKBP10 is sufficient to hinder proliferation of tumor cells growth [ 18 – 20 ]. In coincidence with these observations, our study showed that FKBP10 highly expressed in glioma tissues, and knockdown of FKBP10 could inhibit the proliferation of glioma cells both in vitro and in vivo.…”

“…Nintedanib approved for idiopathic pulmonary fibrosis therapy significantly could down-regulate FKBP10 expression in IPF fibroblasts [ 17 ]. Besides, FKBP10 upregulation has been observed in KRAS mutation-induced lung adenocarcinoma, colorectal cancer renal cell carcinoma, gastric cancer and knockdown of FKBP10 expression could reverse the malignant phenotype, especially proliferation ability [ 18 – 21 ]. Thus, FKBP10 is an important molecule in cell biology activities and a potential therapeutic target with therapeutic drug.…”

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

“…27 However, compared with benign tumor cells and ovarian epithelial cells, the expression of FK506-binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells. 28 FKBP10 is highly expressed in GC, and is a poor prognostic factor for GC; 15 however, the specific mechanism underlying these actions still remain unclear.…”

“…Studies have shown that FKBP10 is highly expressed in a variety of tumors, that it promotes tumor progression and is a poor prognostic factor for tumors, such as kidney, 12 lung 13 and prostate cancer. 14 Online data have shown that FKBP10 is a poor prognostic factor for GC, and that it participate in regulating cell adhesion of GC; 15 however, its specific mechanisms in GC are still unclear. In this study, we performed differential expression gene screening on four independent GC databases, and verified the prognostic effects of 89 consistently up-regulated genes, finally obtaining 12 prognostic genes.…”

The evolving role of ribosomes in the regulation of protein synthesis

“…These results indicate a mechanism relying on the ribosome binding protein, FKBP10, adapted by cancer cells to support their growth by an increase in the protein synthesis. Hence, this could be a promising target for new anticancer therapy (Liang et al, 2019).…”