Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival.

Peter Würl,Matthias Kraus,Helge Taubert,Thomas Greither,Martin S Staege,Lea I Ohm,Maria Giebler,Sindy Blauschmidt

doi:10.3389/fmicb.2018.00211

Abstract

A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients’ prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated (rS = 0.5; p = 6.4 × 10-9; Spearman’s rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival (p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients’ prognosis.

Highlights

Soft tissue sarcomas (STSs) are a heterogeneous group of tumors classified by the somatic tissue they resemble, with over 50 subtypes that can be distinguished (Ducimetière et al, 2011)
human endogenous retrovirus (HERV)-F mRNA expression was detected in 120 patients sarcoma specimen with a mean expression of 6.0
We demonstrated that a robust mRNA expression of HERV-K and HERV-F in a cohort of 120 soft tissue sarcoma (STS) samples is detectable, and that the expression of HERV-K and HERV-F is correlated with clinicopathological features and hypoxia-related gene expression

Summary

Introduction

Soft tissue sarcomas (STSs) are a heterogeneous group of tumors classified by the somatic tissue they resemble, with over 50 subtypes that can be distinguished (Ducimetière et al, 2011). Human endogenous retroviruses (HERVs) are a class of retroviral sequences acquired during evolution by integration of viral genes in the host genome. They became non-infectious by mutation or loss of relevant genes for replication or virus release (Vargiu et al, 2016). They comprise an estimated 8% of the human genome (Lander et al, 2001), and at least independent families based on their homology to known mammalian retroviruses exist (Griffiths, 2001)

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