Correlation and prognostic value of osteopontin and Bcl-2 in hepatocellular carcinoma patients after curative resection

Deng,Biao; Zhang,Xiao-Fei; Zhu,Xu-Chao; Huang,Hua; Jia,Hu-Liang; Ye,Qing-Hai; Dong,Qiong-Zhu; Qin,Lun-Xiu

doi:10.3892/or.2013.2737

Correlation and prognostic value of osteopontin and Bcl-2 in hepatocellular carcinoma patients after curative resection

Authors:
- Biao Deng
- Xiao-Fei Zhang
- Xu-Chao Zhu
- Hua Huang
- Hu-Liang Jia
- Qing-Hai Ye
- Qiong-Zhu Dong
- Lun-Xiu Qin
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Affiliations: Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R. China
Published online on: September 19, 2013 https://doi.org/10.3892/or.2013.2737
Pages: 2795-2803

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Abstract

Osteopontin (OPN) may facilitate tumorigenesis and metastasis through prevention of tumor cells from apoptosis. Although previous studies have suggested involvement of enhanced Bcl-2 protein family expression, the role of OPN together with Bcl-2 in hepatocellular carcinoma (HCC) remains unknown. In this study, we used western blotting to detect the OPN and Bcl-2 expression levels in cell lines with different OPN backgrounds and HCC tissues, and tumor tissue microarrays to examine OPN and Bcl-2 expression levels in 454 HCC cases. The Kaplan-Meier method and log-rank test were applied to investigate the predictive values of OPN and Bcl-2 in HCC patients. In vitro assays indicated that OPN expression increased concordantly with increasing metastatic potential in MHCC97-H, MHCC97-L, HepG2 and SMMC-7721 cell lines by western blotting, whereas Bcl-2 expression declined. In addition, Bcl-2 was highly upregulated in OPN knockdown MHCC97-H cell lines. Furthermore, in HCC tissues, it was confirmed that OPN levels were also significantly higher in recurrent tumor tissues compared to non-recurrent tissues by western blotting (p<0.001), whereas the contrary occurred in Bcl-2 (p=0.046). Using immunohistochemistry analysis, patients with higher OPN levels had significantly shorter median survival time and recurrence time compared to the lower ones, although the opposite occurred in Bcl-2 levels. Of note, when OPN and Bcl-2 were combined, we found that the co-index of OPN/Bcl-2 was an independent prognostic factor for both overall survival (p<0.001) and time to recurrence (p<0.001). Our findings demonstrate that OPN/Bcl-2 expression is a promising independent predictor of recurrence and survival in HCC. Additionally, Bcl-2 levels may be regulated by OPN in the HCC microenvironment.

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