Differential expression of mRNA 3′-end isoforms in cervical and ovarian cancers

Abstract

Early diagnosis and therapeutic targeting are continuing challenges for gynecological cancers. Here, we focus on cancer transcriptomes and describe the differential expression of 3′UTR isoforms in patients using an algorithm to detect differential poly(A) site usage. We find primarily 3′UTR shortening cases in cervical cancers compared with the normal cervix. We show differential expression of alternate 3′-end isoforms of FOXP1, VPS4B, and OGT in HPV16-positive patients who develop high-grade cervical lesions compared with the infected but non-progressing group. In contrast, in ovarian cancers, 3′UTR lengthening is more evident compared with normal ovary tissue. Nevertheless, highly malignant ovarian tumors have unique 3′UTR shortening events (e.g., CHRAC1, SLC16A1, and TOP2A), some of which correlate with upregulated protein levels in tumors. Overall, our study shows isoform level deregulation in gynecological cancers and highlights the complexity of the transcriptome. This transcript diversity could help identify novel cancer genes and provide new possibilities for diagnosis and therapy.