Proteomic and transcriptomic profiling in exosomes derived from HPV-positive head and neck cancer.

It is well-established that the persistence of human papillomavirus (HPV) infections leads to viral DNA integration into the host genome and has been reported to be associated with the alteration of the exosome cargo contents. More importantly, our previous studies as well as others have demonstrated that the presence of HPV oncoprotein/DNA in exosomes isolated from HPV-positive head and neck cancer (HNC) patients, further supporting a vital role of exosomes in mediating the HPV transmission and carcinogenesis. Here, we reported that proteomic and transcriptomic signatures differed in exosomes derived from HPV-negative and HPV-positive HNC cells, as evidenced by 4D-microDIA quantitative proteomics analysis and small RNA sequencing analysis, respectively. Meanwhile, differential exosomal proteins and miRNAs in exosomes derived from HPV-positive HNC cells were highly clustered with multiple signalling pathways related to HPV infection/viral carcinogenesis. Importantly, receiver operating characteristic (ROC) analysis indicated that the combination of HPV-related proteins (eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2), NF-κB p65 (RELA)) and miRNA (miR-130b) as a panel can discriminate the HPV-positive HNC patients from controls (Area under the curve (AUC) = 0.993, Sensitivity 95 % and Specificity 100 %) as well as between HPV-negative and -positive HNC patients (AUC = 0.781, Sensitivity 81 % and Specificity 67 %) based on the TCGA-HNC dataset. In summary, our findings may offer new insights into the key molecular cargo loading into HPV-enriched exosomes, which could potentially underpin the future design of novel diagnostic and prognostic approaches for predicting HPV-positive HNC.