Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer

Abstract

BackgroundThe FK506-binding protein (FKBP) is a family of intracellular receptors that can bind specifically to the immunosuppressant FK506 and rapamycin. Although FKBPs play crucial roles in biological processes and carcinogenesis, their prognostic value and molecular mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear.MethodsUsing pan-cancer data from The Cancer Genome Atlas (TCGA) and public databases, we analyzed the expression and correlation of FKBPs in 33 tumor types. Survival and Cox regression analyses were employed to explore the prognostic value of FKBPs. The relationship with tumor microenvironment and stemness indices was taken into account to evaluate the function of FKBPs. We constructed a risk score model to predict the prognosis of patients with ccRCC. The receiver operating characteristic (ROC) curve was performed to further test the prognostic ability of our model. Nomogram, joint effects analysis, and clinical relevance were performed to assist the clinician. Gene set enrichment analysis (GSEA) and cell line experiments were performed to investigate the function and molecular mechanisms of FKBPs in patients with ccRCC. Paired clinical specimens and multi-omics analysis were used to further validate and explore the factors affecting gene expression in ccRCC patients.ResultsThe expression levels of FKBP10 and FKBP11 were higher in ccRCC tissues than in normal tissues. The alteration in expression may be because of the degree of DNA methylation. Increased expression levels of FKBP10 and FKBP11 were associated with worse overall survival (OS). More importantly, GSEA revealed that FKBP10 is mainly involved in cell metabolism and autophagy, whereas FKBP11 is mainly associated with immune-related biological processes and autophagy. Cell Counting Kit 8 (CCK-8) and Transwell assays revealed that knockdown of FKBP10 and FKBP11 inhibits proliferation, migration, and invasion of the ccRCC cell line.ConclusionFKBP10 and FKBP11 play important roles in ccRCC phenotypes and are potential prognostic markers as well as new therapeutic targets for patients with ccRCC.

Development of a Phagocytosis-Dependent Gene Signature to Predict Prognosis and Response to Checkpoint Inhibition in Clear-Cell Renal Cell Carcinoma

“…Whereas FKBP11 has not been reported in phagocytosis, immunosuppression of FK506 is vastly applied clinically in organ transplantation ( 44 ). Notably, an in-silico study using datasets overlapping ours also showed a similar prognostic role of FKFB11 in ccRCC ( 45 ). Neither MS4A14 nor KDELR3 was reported related to phagocytosis, and the genes are functionally distant from ADCP in previous studies.…”

Identification of novel prognostic biomarkers for osteosarcoma: a bioinformatics analysis of differentially expressed genes in the mesenchymal stem cells from single-cell sequencing data set

“…FKBP11 belongs to the superfamily of FK-506 binding protein and is located on chromosome 12q13.12 with 8 exons. Studies have shown that FKBP11 is upregulated in melanoma, hepatocellular carcinoma, and renal carcinoma (28)(29)(30). Mechanistic studies have revealed that FKBP11 promotes cell proliferation and tumorigenesis via protein 53-related pathways in oral squamous cell carcinoma (31).…”

A Novel Biomarker, FKBP10, for Poor Prognosis Prediction in Patients with Clear Cell Renal Cell Carcinoma

“…It has been widely reported that fibroblast FKBP10 is expressed at a higher level in idiopathic pulmonary fibrosis tissue compared with normal lung tissue, while knockdown of FKBP10 can reduce the synthesis of collagen and reduce the migration of fibroblasts [21]. Also, some studies have found higher expression levels of FKBP10 in CcRCC tissues than in normal tissues [22]. In addition, it has been found that FKBP10 can be used as a new biomarker for bioinformatics analysis and in vitro experiments of gastric cancer prognosis and lymphatic metastasis [18].…”