In-depth bioinformatic study of the Bcl-xL/Bcl2L1 gene in patients with pancreatic cancer

Abstract

Introduction: Pancreatic cancer represents one of the leading causes of cancer-related mortality, with most of the cases being diagnosed with pancreatic ductal adenocarcinoma (PDAC). In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial. The purpose of the current study was to investigate the differential gene expression profile of the BCL-xL gene network in patients with PDAC, given its well-known role in certain hallmarks of cancer, such as apoptosis and cell proliferation. Methods: In silico techniques were used to construct the interactome of the Bcl-xL network, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and uncover the related molecular functions and the regulating miRNAs. Results: Transcriptomic data of one microarray dataset was included, incorporating 130 samples (69 PDAC samples and 61 adjacent non-tumor samples). The nucleotide sequential analysis demonstrated one CpG islands [length: 513 (1, 513)] related to BCL-xL, using the following criteria: Observed/expected ratio >0.60; percent C + percent G >50.00; length >200. BCL-xL was overexpressed in patients with PDAC (p < 0.001) and was associated with an excellent discrimination level (AUC: 0.83 [95% Confidence Intervals: 0.76, 0.90]; p < 0.001). It also estimated well the PDAC incidence (O:E=1). The goodness of fit test was also positive with a low Tjur’s R squared (Tjur’s R squared=0.31). Consequently, BCL-xL was associated with excellent discrimination and calibration traits, thus presenting as a potential biomarker for PDAC. Finally, gene set enrichment analysis indicated that the members of the hsa-miR-296-5p, hsa-miR-6836-5p, hsa-miR-6132, hsa-miR-27a-5p, and hsa-miR-6773-5p miRNA families are important regulators of Bcl-xL. Conclusions: These outcomes demonstrate Bcl-xL as a potential biomarker regarding PDAC.