| Autor: |
Sionakidis, Aristeidis, Lalagkas, Panagiotis Nikolaos, Malousi, Andigoni, Vizirianakis, Ioannis S. |
| Předmět: |
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| Zdroj: |
Clinical & Translational Discovery; Oct2023, Vol. 3 Issue 5, p1-15, 15p |
| Abstrakt: |
Background: Pancreatic ductal adenocarcinoma (PDAC) is the most frequently diagnosed form of pancreatic cancer worldwide. PDAC is associated with a poor survival rate mainly due to the disease being usually diagnosed at late stages. Methods: Publicly available gene expression data from 10 studies with tumour tissue (448 samples) and/or blood samples (128 samples) from PDAC patients were pooled together and analyzed for the identification of stage-specific and global diagnostic markers using differential gene expression analysis. The list of statistically significant (𝑝𝑎𝑑𝑗 < 0.05) differentially expressed genes were used to carry out enrichment analysis via active subnetworks and miRNA enrichment analysis. We then used the results from these analyses to identify the most significant genes and pathways and map these to marketed drugs’ pharmacological targets. The same process was replicated for studies with blood samples and results were compared to those from the tissue analysis. A set of consistently deregulated genes (pancreatic tumour signature, PTS) in both tissue and blood samples was derived and validated in external cohorts and The Cancer Genome Atlas (TCGA) data. Results: Notable gene expression deregulation was found in all tumour stages with significant overlap. We identified 820 consistently deregulated genes (PTS) in tissue samples of all stages and blood samples. Active subnetwork analysis revealed enriched ribosome, proteasome, adherens junction and cell cycle pathways across all stages and blood samples. Our findings suggest that microRNA (miRNA) contribution to PDAC pathology plays a significant role and is probably mediated by distinct miRNAs across stages of PDAC. Stage-specific enriched miRNAs with diagnostic potential included miR-21, miR-29, miR-124 and miR30, for stages 1–4, respectively. By investigating the pharmacogenetic interactions of the identified targets with clinically approved drugs, we outline potential paths for personalized interventions. Importantly, the PTS showed a significant association with survival in TCGA data. Conclusion: Thus, we present a compilation of protein-coding markers and miRNAs that hold potential as a diagnostic tool for the early detection of PDAC, as well as for designing novel therapeutic strategies aimed at improving patient outcomes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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