Identification of alternative splicing characteristic associated with clear-cell ovarian cancer from paired normal and tumor tissues

Abstract

Alternative splicing of messenger RNAs (mRNAs) is a common and conserved biological process in eukaryotes. The aberrancy or disruption of different alternative splicing forms may cause alterations of cell functions and result in diseases. It is proposed that alternative splicing may play a critical role in the mechanisms of carcinogenesis. By studying a large dataset in The Cancer Genome Atlas database, a recent study showed that alternative splicing, particularly exon-exclusion, is a powerful prognosis factor in serious subtype of ovarian cancer. However, the characteristics of alternative splicing has not been studied in other subtypes. In this study, we focus on the alternative splicing events, i.e. single exon-inclusion or -exclusion, in clear-cell ovarian cancer subtype. The subtype appears to have particularly high incidence in Asians comparing to Europeans and Americans and tend to be drug resistant. Transcriptomes were obtained from tumors and their paired-normal tissues from five patients. PSI-values, which represent the proportions of alternative splicing events of an exon, were calculated in both tumor and paired-normal tissues. Differences of PSI-values between tumors and paired-normal were examined by a significant test based on Conditional Beta Regression model. In total, we identified ~200 exons covering 52 genes with significant differences between cancer and paired-normal tissue (p <; 0.001) including gene ERP29 and PAM which were previously identified in serous subtypes.