Human Endogenous Retroviruses-K (HML-2) Expression Is Correlated with Prognosis and Progress of Hepatocellular Carcinoma

Abstract

Background. The association between human endogenous retroviruses-K (HERV-K) (HML-2) and human disease, including a variety of cancers, has been indicated. However, the function of HERV-K (HML-2) in the progression of hepatocellular carcinoma (HCC) still remains largely unclear. Methods. We detected the expression of HERV-K (HML-2) in 84 HCC tissues and adjacent nontumor tissues by quantitative real-time PCR (qRT-PCR) and analyzed its correlation with the clinical parameters. Result. The HEVR-K level was significantly increased in HCC compared with adjacent normal tissues (P < 0.01) which was proved to be significantly associated with cirrhosis (P < 0.05), tumor differentiation (P < 0.05), and TNM stage (P < 0.05). Moreover, the high expression of HERV-K (HML-2) had a poorer overall survival than patients with lower expression by a Kaplan-Meier survival analysis (P < 0.01). The multivariate Cox regression analysis indicated that the level of HERV-K (HML-2) was an independent prognostic factor for the overall survival rate of HCC patients. Receiver operating characteristic (ROC) curves demonstrated the diagnostic accuracy of HERV-K (HML-2) expression in HCC (AUC = 0.729, 74.7% sensitivity, and 67.8% specificity). Conclusions. Our results suggested that upregulation of HERV-K (HML-2) in HCC patients was significantly related to cancer progression and poor outcome, indicating that HERV-K (HML-2) might be a novel candidate prognostic biomarker for HCC.

Figure 1

Increased HERV-K (HML-2) expression in HCC tissues and the association with clinical parameters of HCC patients. The value of relative expression was detected by the value of −log of 2^−ΔCt. (a) HERV-K (HML-2) expression level in tumor tissues was significantly higher than in nontumor tissues, P < 0.0001. (b) Differentiation: a: high/moderate; b: low; TNM stage: a: I-II; b: III-IV; Cirrhosis: negative/positive. Results are expressed as mean ± SD. All data were analyzed using Student's t-test. ^∗ P < 0.05 and ^∗∗ P < 0.01.

Figure 2

High level of HERV-K (HML-2) predicts poor survival in HCC. Patients with higher HERV-K (HML-2) expression (n = 42) showed reduced survival time compared with patients with lower levels of HERV-K (HML-2) expression (n = 42) by the Kaplan-Meier survival curve analyses (log-rank test: P < 0.01).

Figure 3

ROC curves of HERV-K (HML-2) expression. (a) HERV-K (HML-2) was considered to be a valuable parameter in the prediction of HCC (AUC = 0.730, 95% CI: 65.21%–80.55%, and P < 0.0001). (b) The predicative value of HERV-K (HML-2) for differentiation of HCC resulted in AUC of 0.678 (95% CI: 50.70%–83.65%, P = 0.041). (c) The significant diagnostic value of HERV-K (HML-2) for TNM stage of HCC (AUC = 0.645, 95% CI: 51.79%–77.27%, and P = 0.030).