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

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.

Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

“…The role of HERVH as biomarker has been discussed in several cancers, including colorectal carcinoma, prostate cancer and lung cancer. 62 , 63 , 64 Further experiments, at the nucleic acid or protein level, are needed to verify whether HERVH is an effective diagnostic biomarker. HHLA2, a newly discovered immune checkpoint belonging to B7 family, is thought to be derived by HERVH.…”

HERV-K Envelope Protein Induces Long-Lasting Production of Autoantibodies in T1DM Patients at Onset in Comparison to ZNT8 Autoantibodies

“…Of note, in contrast to antibodies against HERV-W, we observed a constant Abs response against HERV-K Env 19–37 that remains over time, up to 5 years of disease, and then decreases. HERV-K is probably not involved in the pathogenesis of T1DM but is related to a general HERV-K expression in other inflammatory conditions; however, this has to be confirmed [ 33 , 34 , 35 ].…”

Bisphenols induce human genomic damage and modulate HERVs/env expression

“…One of these is the HERV‐R/ env gene, whose transcriptional downregulation has been reported in cases of choriocarcinoma (Rote et al, 1998 ). In particular, significant antibody response was observed against HERVs envelope ( env ) epitopes detected in patients with diabetes and other diseases (Manca et al, 2022 ; Noli et al, 2021 ; Simula et al, 2021 ). In 2009, a study revealed that the presence of these env viral proteins could contribute to the development of cancer cells (Balada et al, 2009 ).…”