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

Abstract

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.

Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line

“…In the present study, the protein expression levels of caspase-3 and caspase-9 were significantly upregulated in the GnT-V-knockdown SMMC-7721/R cells, which was consistent with the results of a previous study performed in H7721 human HCC cells (21). Furthermore, the proteins Bcl-2 and Bax are also essential for cell apoptosis, functioning as the predominant controller and mediator of apoptosis, respectively, and the ratio of Bcl-2 to Bax is a key factor determining whether the switch to apoptosis is made (24,25). The results of the present study demonstrated that the protein expression level of Bcl-2 was downregulated, whereas that of Bax was upregulated.…”

Role of osteopontin in the pathophysiology of cancer

“…Also patients with higher OPN levels had significantly shorter median survival time and recurrence time compared to the ones with lower OPN levels. It was also observed that co-index of OPN/Bcl-2 levels was an independent prognostic factor for both overall survival and time to recurrence in this cancer type (Deng et al, 2013). …”

Molecular signatures in hepatocellular carcinoma: A step toward rationally designed cancer therapy

“…They identified 6 proteins that were uniquely upregulated in early recurrence that included extracellular signal‐regulated kinase 1 (ERK1), protein kinase G (PKG), apoptotic protease activating factor 1 (Apaf1), B‐cell leukemia X (Bcl‐X), Abelson murine leukemia viral oncogene (c‐abl), protein inhibitor of activated STAT 1 (PIAS1), and PIAS2. It has been demonstrated that both ERK and Bcl‐X correlate with a poor prognosis in HCC . Multiple ERK inhibitors are currently in early phase clinical trials for solid gastrointestinal malignancies and may be of potential value in the treatment of HCC.…”

“…It has been demonstrated that both ERK and Bcl-X correlate with a poor prognosis in HCC. 94,95 Multiple ERK inhibitors are currently in early phase clinical trials for solid gastrointestinal malignancies and may be of potential value in the treatment of HCC.…”