Giebler Maria, Staege Martin S, Blauschmidt Sindy, Ohm Lea I, Kraus Matthias, Würl Peter, Taubert Helge, Greither Thomas
Center for Reproductive Medicine and Andrology, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Department of Pediatrics I, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Front Microbiol. 2018 Feb 13;9:211. doi: 10.3389/fmicb.2018.00211. eCollection 2018.
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 ( = 0.5; = 6.4 × 10; 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 ( = 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.
迄今为止，人类基因组中已发现了各种各样的内源性逆转录病毒序列，根据与病毒株的序列同源性可分为几个不同的家族。虽然人类内源性逆转录病毒（HERV）元件表达增加已与肝细胞癌、乳腺癌和卵巢癌的不良预后相关，但对于不同HERV元件的表达在一般肉瘤发生以及软组织肉瘤（STS）患者预后方面的影响知之甚少。因此，在本研究中，评估了HERV-K和HERV-F的表达与一组STS患者的临床病理特征以及患者预后之间的关联。通过定量实时PCR对120例患者标本中的HERV-K和HERV-F表达进行了评估。HERV-K和HERV-F表达显著相关（ = 0.5； = 6.4 × 10；Spearman等级双变量相关性）。此外，肿瘤直径与HERV-K和HERV-F表达呈显著负相关。几种缺氧相关RNA如HIF-1α和miR-210的水平与HERV-K和HERV-F表达均呈显著正相关。虽然在生存分析中未检测到HERV表达对疾病特异性生存的影响，但HERV-K表达升高的患者无复发生存期明显缩短（ = 0.014，对数秩分析）。总之，我们首次提供证据表明肿瘤中HERV-K表达增加与STS患者的预后相关。
