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Abstract
Introduction/Background This study investigates the influence of wound healing processes on residual tumors during the perioperative period and explore the potential targets and drugs to alleviate the negative effects of wound healing on residual tumors, utilizing mRNA sequencing to analyze changes in a syngeneic mouse model.
Methodology A total of 50 mice were divided into four groups: baseline, and one, two, and three weeks after surgery. Total RNA was collected and sequenced using an Illumina sequencer. Raw sequences were aligned, mapped, and counted using the NCI Genomic Data Commons (GDC) RNA sequencing pipeline. Differentially expressed genes (DEGs) were analyzed using EdgeR. The list of DEGs representing the transcriptomic profile of each group was employed as a query signature for the transcriptome-based drug discovery platform, REMEDY.
Results We were able to obtain 48 tumor tissue samples, and among these, a total of 29 samples with an RNA integrity number (RIN) of 6 or higher were used for mRNA analysis. On the first day after surgery, among the wounding-specific mRNA changes, 140 genes were observed to be upregulated and 14 genes downregulated. Gene ontology (GO) analysis revealed the highest expression in genes related to muscle contraction (GO:0006936). One-week after surgery, 366 genes were upregulated and 104 genes downregulated, with the highest expression observed in aerobic electron transport chain (GO:0019646), mitochondrial ATP synthesis coupled electron transport (GO:0042775), and mitochondrial respiratory chain complex assembly (GO:0033108). Finally, in the two-week post-surgery samples, 236 genes were upregulated, and 53 genes downregulated, with the highest expression related to cyclic-nucleotide-mediated signaling (GO:0019935). In the analysis using the REMEDY, MG-132, bortezomib, and cucurbitacin-i were predicted to effectively reduce mRNA changes one week after surgery, thereby enhancing the anti-tumor effect.
Conclusion This study highlights the significant impact of wound healing processes on residual tumors in advanced ovarian cancer during the perioperative period.
Disclosures To the best of our knowledge, the named authors have no conflict of interest, financial or otherwise.
