Abstract
The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.
Highlights
The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation
HMGB1 protein was localized in the nucleus, while some cytoplasmic localization was observed in colorectal cancer (CRC) and colorectal adenoma tissue samples (Fig. 1)
Data about the subcellular localization of HMGB1 in CRC is only available from two individual reports, both of which involve small samples of CRC tissue and neither has clarified the correlation between different subcellular localization sites of HMGB1 and their clinicopathologic prognostic s ignificance[16,17]
Summary
The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). Abbreviations IHC Immunohistochemistry CRC Colorectal cancer HMGB1 High-mobility group box-1 RFS Relapse-free survival OS Overall survival. The research has failed to clarify any association between different subcellular locations of HMGB1 and their clinicopathologic prognostic significance. We examined the expression of HMGB1 in different subcellular locations (nucleus and cytoplasm) and analyzed the association between them. This study aimed to determine the clinicopathologic and prognostic significance of different subcellular locations of HMGB1
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