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RNA-Seq Analysis of Pancreatic Ductal Adenocarcinoma: Epigenetic Adaptation in Response of Drug Treatment


Chemotherapy is the dominant treatment approach to many cancers. For decades, Gemcitabine (GEM) has been used as the first-line therapy for pancreatic ductal adenocarcinoma (PDAC), one of the most fatal solid tumor, but its competence is disappointingly constrained byintrinsic or adaptive resistance. The mechanisms beneath such resistance have been intensively studied with great efforts and its correlations with many genes and pathways have been found. However, our knowledge has not been unified to provide abundant information for major advances, since the whole landscape in which drug adaptation and gene expressions are associated is not yet clear. Moreover, little had we known about the initiation of adaptation, which makes it more difficult to define better therapies and achieve better clinical outcomes.

Recently, epigenetic alterations have become potential prognostic biomarkers and offered vast options for PDAC detection. Previously, we had observed different histone 3 lysine 9 trimethylation (H3K9me3) patterns among GEM sensitive and resistant PDAC cells during the GEM treatment, suggesting the role of histone modification in GEM resistance initiation and exhibition. In this paper, we would provide our analysis workflow to identify the candidate genes that might be modulated by H3K9me3 upon GEM treatment, and predict how they dynamically affect GEM sensitivity. Our results would be considered as a general framework to construct the regulatory network from epigenetic drug response to transcriptomic plasticity, and discover new opportunities for therapeutic development.

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