Association of Upregulated HMGB1 and c-IAP2 Proteins With Hepatocellular Carcinoma Development and Progression

Abstract

Background:Hepatocellular carcinoma (HCC) is one of the most important health problems in China.Objectives:This study analyzed expression of high-mobility group protein B1 (HMGB1) and inhibitor of apoptosis protein-2 (c-IAP2) proteins in HCC compared to paired para-tumor tissue samples to assess the association with HCC pathogenesis and progression.Materials and Methods:Sixty-eight HCC and para-tumor tissue samples were collected for Western blot, qRT-PCR and immunohistochemical analyses of HMGB1 and c-IAP2.Results:HMGB1 and c-IAP2 proteins were highly expressed in HCC tissue samples [85.3% (58/68) and 82.4% (56/68), respectively] compared to para-tumor tissue samples [32.3% and 27.9%, respectively]. Furthermore, expression of HMGB1 was significantly associated with enhanced c-IAP2 expression in HCC tissue samples (r = 0.878, P < 0.01). Expression of HMGB1 was associated with tumor multiplicity and size, alpha-fetoprotein (AFP) level and advanced TNM stage, while expression of c-IAP2 was associated with tumor size, AFP level and advanced TNM stage.Conclusions:Expression of HMGB1 and c-IAP2 proteins was associated with HCC development and progression, and the expression of HMGB1 and c-IAP2 proteins in HCC were significantly associated with each other. Additionally, these proteins may show promise as biomarkers to predict HCC progression.

Effects of HMGB1 Polymorphisms on the Susceptibility and Progression of Hepatocellular Carcinoma

“…Wang et al, also has been summarized the HMGB1 signaling pathway in HCC development 33 . In addition, Bi et al, found that HMGB1 upregulated with HCC progression 34 . However, the correlation between HMGB1 polymorphisms and HCC progression is never discussed.…”

Increased HMGB1 expression correlates with higher expression of c-IAP2 and pERK in colorectal cancer

“…Bi et al also found the expression of HMGB1 and c-IAP2 proteins in cancer to be significantly associated with each other. [18] HMGB1 expression had a positive correlation with c-IAP2 and pERK, suggesting that HMGB1 may affect the expression of c-IAP2 via the activity of pERK. Recent research has shown that HMGB1 binds to CXCR4, which activates multiple signaling pathways, including ERK.…”

The Role of HMGB1 Signaling Pathway in the Development and Progression of Hepatocellular Carcinoma: A Review

“…For HCC, some cell cycle proteins and proliferation cytokines are central in the proliferation, such as cyclin D1 and proliferating cell nuclear antigen (PCNA). HMGB1 not only increased cyclin D1 and PCNA to induce the proliferation of HCC [ 47 ], but also regulates for tumor multiplicity and size, alpha-fetoprotein (AFP) level and advanced TNM stage in HCC [ 48 ], indicating HMGB1 could be used as a biomarker for HCC diagnosis which deserves further study [ 49 ].…”