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Volume 19   Issue 1   Year 2024
Alternative Splicing in Pancreatic Ductal Adenocarcinoma Leads to Dysregulated Immune System

Fatimah A. Abdul Jabbar1, Rawaa AlChalabi1, Ahmed Yaseen AL-Tarboolee1, Semaa A. Shaban2, Ahmed AbdulJabbar Suleiman3

1College of Biotechnology, AL-Nahrain University, Jadirya, Baghdad, Iraq
2College of Sciences, Tikrit University, Tikrit, Iraq
3College of Science, University of Anbar, Ramadi, Anbar, Iraq

Abstract. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that poses a significant global health threat, marked by a substantial increase in prevalence and mortality rates. Accounting for 90 % of pancreatic cancer cases, PDAC carries a dismal prognosis, and current therapeutic approaches, including immunotherapy, face challenges due to poor immunogenicity. This study aimed to discover differentially expressed immune genes shared between PDAC and normal samples from two datasets obtained from the NCBI GEO Dataset. The RNA-seq pipeline was employed for gene expression analysis, and enrichR facilitated functional enrichment analysis of biologically and statistically significant genes. Predictions of immune infiltration cells and corresponding genes, along with their immune responses, were made using the ScType database and the immunedeconv package, respectively. Verification of gene expression levels was conducted through GEPIA2, Expression Atlas, and literature review. Additionally, isoform-switching analysis of dysregulated genes aimed to uncover alternatively spliced pathogenic isoforms in PDAC. Notably, four immune genes (EPHA2 upregulated, GNG11, CRHBP, and FCER1A downregulated) were found to be common in both datasets and were highly implicated in PDAC. The dysregulated immune genes influenced molecular functions, including protein binding, transmembrane receptor protein tyrosine kinase activity, protein tyrosine kinase activity, and cadherin binding for upregulated genes. Downregulated genes were associated with GTPase activity and ribonucleoside triphosphate phosphatase activity. This study suggests these immune genes as potential prognostic biomarkers for effective PDAC treatment. However, further investigations are essential to unravel the functional perspectives of potential isoforms.


Key words: PDAC, alternative-spliced genes in PDAC, immune-infiltrating genes in PDAC, PDAC dysregulated immune genes, PDAC immune therapeutic biomarkers.

Table of Contents Original Article
Math. Biol. Bioinf.
doi: 10.17537/2024.19.15
published in English

Abstract (eng.)
Abstract (rus.)
Full text (eng., pdf)
Supplementary data


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