BORIS, brother of the regulator of imprinted sites, is aberrantly expressed in hepatocellular carcinoma

Abstract

Background: The brother of the regulator of imprinted sites (BORIS) is a novel member of the cancer testis antigen gene family, which are normally expressed only in spermatocytes, but abnormally activated in different malignancies.

Aim: The aim of this study was to explore the expression of BORIS in hepatocellular carcinoma (HCC) and its correlation with the clinicopathologic features and prognosis of HCC.

Methods: We investigated BORIS expression in HCC cell lines and 105 primary HCC clinical surgical specimens using real-time polymerase chain reaction and Western blot analysis. We further examined the correlation of BORIS with a liver stem cell marker (CD90) in HCC tissues by histochemical double staining. The correlation of BORIS with clinicopathologic features and prognosis of HCC was analyzed using patient data.

Results: The expression of BORIS was found in SMMC-7721, BEL-7402, and Huh-7, but not in hep-G2 cells. The expression rate of BORIS was significantly higher in the HCC tissues than in the adjacent noncancerous tissues (p=0.000). BORIS expression was correlated with the tumor size (p=0.000), CD90 expression (p=0.000), and satellite nodule (p=0.000). Kaplan-Meier survival curves showed that patients with positive expression of BORIS had lower overall survival rate (p=0.003).

Conclusions: Our data indicate that BORIS may be an auxiliary diagnosis index and a novel favorable prognostic indicator of HCC.

FIG. 1.

Detection of the brother of the regulator of imprinted sites (BORIS) mRNA and protein in four human liver cancer cell lines by reverse transription–polymerase chain reaction (A) and Western blot (B). Expression of BORIS mRNA and protein in SMMC-7721 (lane 2), BEL-7402 (lane 3), and Huh-7 (lane 4), but not in hep-G2 (lane 5). Human testicular tissues (lane 1) were used as positive control; normal liver tissue (lane 6) was used as nonmalignant negative control.

FIG. 2.

The immunoreactivity score (IRS) values for 34 BORIS-positive samples (2.43±0.51) in paracancer tissues were lower than 58 BORIS-positive samples (5.22±0.53) in hepatocellular carcinoma (HCC) tissues (p=0.01).

FIG. 3.

Detection of BORIS and CD90 protein in normal human liver (A, B), HCC (D–J), and normal testicular tissues (C) by immunohistochemistry (IHC) and immunofluorescence. Different residual fluorescence is observed in the same hepatoma carcinoma cell (arrow).

FIG. 4.

Kaplan–Meier survival curves for BORIS-positive group versus BORIS-negative group in 105 patients with HCC showed a highly significant separation (p=0.003, log-rank test).