Novel microRNA multivariate biomarkers of response to immunotherapy against HPV E6 oncogene

Abstract

AbstractCervical cancer is caused by the persistent infection high-risk types of human papillomavirus (HPV) in over 99.9% of cases. To favor malignant transformation, HPV E6 and E7 oncogenes disrupt both p53 and retinoblastoma (Rb) respectively and control microRNA (miR) networks. We have previously demonstrated the therapeutic potential of anti-HPV E6 monoclonal antibodies (mAbs) in experimental models of human cervical cancer; yet the underlying mechanism remains unclear. Here, we sought to determine if anti-HPV E6 mAbs modulate the miR signatures of HPV E6 oncogenes. To this end, we performed qRT-PCR to measure the expression of thirty-four miRs and found that univariate analysis is not able to identify novel interactions characteristic of complex biological systems. Thus, we utilized partial least squares discriminant analysis (PLSDA) to identify signatures of co-varying miRs specific to mAb treatment. These miR signatures predictively discriminate between anti-HPV E6 mAb response and control mAb treatment, which may provide mechanistic insight into the action of anti-HPV E6 mAbs.