Transcriptional scenario of altered glycosylation in HPV-associated cervical cancer

Abstract

Background: Cervical cancer is one of the leading malignancies in women of India with high mortality rate and no available targeted therapy. This is due to dearth in understanding of underlying mechanisms regulating cervical carcinogenesis and distinguished behavioral pattern of HPV-associated carcinomas. This study aims to understand association of HPV infection and cervical cancer with aberrant glycosylation, an enabling factor for other hallmarks of cancer. Materials and Methods: DNA and RNA were isolated from biopsy samples of 92 cervical cancer patients. HPV 16 and 18 infection was detected by endpoint Type-Specific PCR. RNA samples were processed for expression analysis of HPV 16-E6, HPV 16-E7 and HPV 16-E2 oncogenes. Analysis of the expression of glycosylation transcripts were performed using qPCR. Results: Correlation of HPV infection with transcript levels of ST3GAL3, ST6GAL1, FUT5 and FUT8 was observed. In HPV 16 and 18 positive patients, the transcript levels of ST3GAL3, ST6GAL1 and FUT5 were higher while FUT8 transcripts levels showed down-regulation. Conclusion: This data depicts hyper-glycosylation patterns associated with HPV infection. HPV-associated cancers showed down regulation of core fucosylation and up-regulation of ST3GAL3, ST6GAL1 and FUT5. The behavioral pattern for HPV-associated cancer could be due to its differential association with altered glycosylation.