Genes associated with platinum-resistance in platinum-resistant ovarian cell line

Background: In this study the authors aimed to identify genes associated with platinum-resistance in platinum-resistant ovarian cell line. Materials and Methods: The transcriptome profile dataset ERA033498 was downloaded. Clean sequencing reads were mapped to human hg19 genome using TopHat. After filtering, reads were then annotated using ANNOVAR tool. Gene expression level was estimated by the value of Fragments Per Kilobase of transcript per Million mapped reads (FPKM) using Cufflinks. R/Limma package was used to identify differentially expressed genes (DEGs) between the platinum-sensitive and -resistant cell lines in each patient, with the threshold of |log2(fold change)|> 2 and q-value < 0.05. Then, functional annotation and pathway enrichment analysis of DEGs was performed. A protein-protein interaction (PPI) network was also built using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), followed by module analysis, and further functional annotation of the sub-network genes. Results: Quality sequencing reads was collected from each sample, with the lowest alignment rate of 95.38%. Totally, 304 DEGs were commonly identified from the two patients, including 247 up-regulated. Four IFIT family members were observed to be up-regulated. STAT1, MX1, DDX58, XAF1, and IFIH1 were the top five hubs with the highest connection degrees in the PPI network. STAT1 may affect platinum-resistance via influenza A, herpes simplex infection, hepatitis C and measles pathways; IFIH1 may function via RIG-I-like receptor signaling pathway, influenza A, herpes simplex infection, and measles pathways; IFIT1 via the herpes simplex infection and hepatitis C pathways. Conclusions: STAT1, IFIH1, and the four IFIT family members may be associated with platinum-resistance in ovarian cancer cells.

Ovarian cancer; Platinum-resistance; Functional annotation and pathway enrichment analysis; Protein-protein interaction network; Module analysis.

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