Background
Non-Aids Defining Cancers (NADCs) are the main cause of morbidity and death from non-AIDS events (ENOS) in PLWH, whose death rate is higher than in the general population without HIV infection but who suffer from these same NADCs. However, the mechanisms that explain this are unknown. It has been suggested that exosomes derived from HIV infected cells can promote and enhance cancer in vitro. Herein, we have analyzed the proteomic and miRNA cargo of exosomes from PLWH with active NADC to identify a molecular profile associated to this condition.
Methods
Forty-two participants were included: 11 PLWH on cART (HIV+NADCs–), 11 on cART with NADC (HIV+NADCs+), 10 HIV-uninfected with NADCs (HIV–NADCs+), and 10 healthy volunteers (HC). Size Exclusion Chromatography was employed to isolate plasma exosomes. Protein and miRNAs content of exosomes isolated from plasma were analyzed by liquid chromatography coupled with mass spectrometry (proteins), and by RNAseq in a Miseq System (miRNAs). Canonical discriminant analysis (CDA) was used to identify the molecular profile (miRNA and/or proteins) in the exosome cargo from PLWH with NADCs compared to the other study groups.
Results
A total 599 miRNAs and 317 proteins were detected in the exosomes cargo of study groups. Only those proteins or miRNAs showing differential expression (DE) between the different study groups (130 miRNAS and 133 proteins) were included in the CDA. The CDA was able to completely (100%) discriminate between the four study groups. The CDA for pairs of groups (six different models) was also able to perfectly (100%) discriminate between participants in each group. Moreover, the profile of miRNAs and proteins included in each of the six CDA models was exclusive of each model, suggesting a specific profile of exosomes cargo associated to each study group. Interestingly, the CDA models discriminating between HIV+NADCs+ and HIV–NADCs+ or between HIV+NADCs+ and HIV+NADCs– included different miRNAs and proteins involved in the promotion and progression of cancer (i.e. hsa-miR-1298-5p, hsa-miR-135b-5p, glutathione peroxidase, retinol-binding protein, collagen alpha-1 chain, dermcidin).
Conclusions
Our results show the existence of a specific exosomes cargo associated to concomitant HIV infection and NADCs characterized by increased levels of pro-oncogenic and decreased levels of anti-oncogenic proteins and miRNAs. These results show the existence of a relevant role of HIV infection in the promotion and progression of cancer.
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