Objective

This study aims to comprehensively investigate the expression patterns of FK506-binding protein 3 (FKBP3) within various cancer subtypes and assess its clinical relevance alongside possible biological functions in lung adenocarcinoma (LUAD).

Methods

FKBP3 expression data, together with clinical data from hepatocellular carcinoma (LIHC) specimens, were sourced from The Cancer Genome Atlas (TCGA) database. A comparative evaluation of FKBP3 expression levels across tumor tissues and their corresponding normal controls was conducted using the Wilcoxon rank-sum test. Chi-square testing was used to investigate the relationship between FKBP3 expression levels and clinicopathological features. Evaluation of FKBP3’s prognostic relevance was executed through Cox regression and Kaplan-Meier survival analyses. Furthermore, the relationship linking FKBP3 with immune cell infiltration was investigated.

Results

Pan-cancer analysis revealed that FKBP3 exhibited markedly higher expression across multiple tumor types, showing statistically significant differences observed in bladder cancer (BLCA), breast cancer (BRCA), cervical cancer, colorectal cancer (COAD), esophageal cancer (ESCA), glioblastoma, head, and neck squamous cell carcinoma, kidney clear cell carcinoma (KIRC), LIHC, LUAD, lung squamous cell carcinoma (LUSC), kidney chromophobe (KICH), kidney papillary cell carcinoma, prostate cancer (PRAD), gastric cancer, and thymoma. Subsequent analysis concentrating on LUAD showed that FKBP3 expression levels exhibited marked elevation in both messenger RNA (mRNA) and protein levels in tumor tissues relative to normal tissues. Receiver operating characteristic (ROC) curve analysis revealed robust diagnostic potential of FKBP3 (area under the curve [AUC] = 0.894). Clinicopathological analysis showed that elevated FKBP3 expression levels significantly correlated with pathological N stage and residual tumor status (P < .05). Cox regression analysis established FKBP3 as an independent unfavorable prognostic factor regarding overall survival (OS) in LUAD subjects. A nomogram model was developed utilizing FKBP3 expression for prognostic prediction, which exhibited excellent calibration performance. Furthermore, Kaplan-Meier and time-dependent ROC analyses additionally validated the prognostic significance of FKBP3 in LUAD. Bioinformatics analysis indicated that FKBP3-related genes were markedly enriched within cancer-associated pathways, cellular senescence, and PD-L1/PD-1 signaling pathways. Immune infiltration analysis demonstrated that FKBP3 expression was inversely associated with most immune cells, particularly plasmacytoid dendritic cells (pDCs), mast cells, natural killer (NK) cells, and immature dendritic cells (iDCs), while exhibiting a positive correlation with Th2 cells. These findings indicate that FKBP3 may facilitate immune evasion through regulating the tumor immune microenvironment.

Conclusion

In summary, FKBP3 holds potential diagnostic, and prognostic value in LUAD and may play a role in regulating tumor immune processes, making it a promising therapeutic target.