Dysregulated expression of cell cycle regulators CDC20, PLK1, BUB1, CDC45, CDCA5 in pancreatic ductal adenocarcinoma

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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with five years survival rate less than 5%. In Pakistan, transcriptomic profiling of pancreatic cancer is limited, with most evidence derived from in silico and isolated NGS analyses, highlighting the need for RNA-sequencing-based expression profiling in Pakistani PDAC cohorts. The purpose of this study is to report hub genes that are involved in progression of cancer and can be used as diagnostic and therapeutic markers. Pakistani PDAC RNA-seq dataset was pooled with seven publicly available NCBI-GEO datasets (GSE136569, GSE119794, GSE164665, GSE119224, GSE211398, GSE196009, and GSE40174) to probe common hub genes. The expression of these hub genes in tumor samples was evaluated using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and validated through Whole Exome Sequencing. CDC20, PLK1, BUB1, CDC45, and CDCA5 were concordantly present in seven NCI-GEO Datasets along with Pakistani RNA-seq dataset. These hub genes were upregulated at the initial stages of PDAC. RT-qPCR revealed significant upregulation in Pakistani tumor samples (*P < 0.05, **P < 0.001). WES analysis demonstrates non synonymous pathogenic variants in BUB1. The consistent dysregulated expression of the hub genes across independent NCBI-GEO datasets and the Pakistani RNA-seq cohort suggests their possible robustness across diverse populations and potential utility as broadly applicable biomarkers. These findings offer population-specific insights that may inform future biomarker-guided diagnostic and prognostic stratification of PDAC in Pakistan.
Funding Information
  • Pakistan Council of Scientific and Industrial Research (Ref.SW9HO0DRS-2/2022/3181)

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