HERV-K and HERV-H Env Proteins Induce a Humoral Response in Prostate Cancer Patients.

Maria Antonietta Manca,Elena Rita Simula,Leonardo A Sechi,Massimo Madonia,Stefano Ruberto,Marta Noli,Tatiana Solinas

doi:10.3390/pathogens11010095

Abstract

A higher expression of human endogenous retroviruses (HERVs) has been associated with several malignancies, including prostate cancer, implying a possible use as a diagnostic or prognostic cancer biomarker. For this reason, we examined the humoral response against different epitopes obtained from the envelope protein of HERV-K (HERV-K env-su19–37, HERV-K env-su109–126), HERV-H (HERV-H env-su229–241, HERV-H env387–399) and HERV-W (HERV-W env-su93–108, HERV-W env-su248–262) in the plasma of patients affected by prostate cancer (PCa), and compared to that of benign prostate hyperplasia (BPH) and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN) and healthy controls. A significant antibody response was observed against HERV-K env-su109–126 (p = 0.004) and HERV-H env-su229–241 (p < 0.0001) in PCa patients compared to HCs, BPH and borderline cohorts, whilst no significance difference was found in the antibodies against HERV-W env-su93–108 and HERV-W env-su248–262 in patients with PCa. Our results provided further proof of the association between HERV-K and PCa and added new evidence about the possible involvement of HERV-H in PCa pathogenesis, highlighting their possibility of being used as biomarkers of the disease.

Highlights

Prostate cancer (PCa) is the most common cause of death by cancer in the male population
The detection of antibodies against the selected highly immunogenic peptides derived from different portions of the envelope protein of human endogenous retroviruses (HERVs)-K, HERV-W and HERV-H was carried out by an indirect Enzyme-Linked Immunosorbent Assay (ELISA) assay within the healthy controls (HCs), PCa, benign prostate hyperplasia (BPH) and the borderline cohorts
Fifteen out of 105 (14%) patients with PCa (p = 0.004), 6 out of 74 (8%) patients with PBH, 2 out of 31 (6%) patients of the borderline group, and 6 out of 104 (6%) of the healthy controls were seropositive against HERV-K env-su109–126 (Figure 1D)

Summary

Introduction

Prostate cancer (PCa) is the most common cause of death by cancer in the male population. Np9 plays an intriguing role in the co-activation of β-catenin, ERK, Akt and Notch promoting the growth of human leukemia stem/progenitor cells [16] Both Np9 and Rec have been shown to interact, physically and functionally, with the promyelocytic zinc finger (PLZF) tumor suppressor, and inhibit its role as a transcriptional repressor, leading to c-Myc overexpression and alterations in the expression patterns of c-Myc target genes [17]. The aim of this study was to evaluate the presence of autoantibodies against different epitopes derived from the envelope protein of HERV-K, HERV-W and HERV-H in the plasma of patients with PCa compared to healthy controls (HCs), a cohort of patients with benign prostate hyperplasia (BPH), and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN)

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