Investigating the role of FKBP1A in Pancreatic adenocarcinoma via integrated in silico approach

Abstract

Pancreatic adenocarcinoma (PAAD), the most common type of pancreatic cancer originating in the exocrine cells of the pancreas, is one of the most aggressive malignancies, characterized by rapid growth and a high propensity for metastasis. Worldwide, around 495,000 new cases were recorded in 2020. Around 40,000 new cases are reported each year in developing nations, particularly in India, where the incidence is rising. Among the various biomarkers of PAAD, FKBP1A has emerged as a promising molecular biomarker, due to its elevated expression in white blood cells during early disease stages. FKBP1A is a small protein member of immunophilin family, facilitates appropriate protein folding and acts as a peptidylprolyl cis-trans isomerase (PPIase). Present study aims to investigate the role of FKBP1A in PAAD, its correlation with known biomarkers and its association with tumor progression and patient survival. The transcriptomic data of PAAD patients was extracted from TCGA for assessment and evaluation. The results indicate the 4.21-fold upregulation of FKBP1A in PAAD as compared to normal cells, which was found to be almost constant across all stages of PAAD. The overall survival analysis shows a hazard ratio (HR) of 1.6 and a p-value of 0.028 for the highexpression group, suggesting that patients with high expression of FKBP1A may have less survival. The results also indicate the poor survival of the male patients as compared to the female patients. We also identified the increased risk of disease recurrence in disease-free survival analysis. GLOBOCAN data indicates a rise in pancreatic cancer mortality in India for both sexes. Furthermore, FKBP1A positively correlates with other known biomarkers of PAAD (AREG, SPP1, KRAS, SMAD4, SMAD7, ACVR1B, NCBP2, LGR5, CDK2A). The correlation as well as the interaction analysis suggests that FKBP1A might be a crucial prognostic biomarker for PAAD.