Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, 60 Wu Ning Xi Road, Dongyang, 322100, Zhejiang, People's Republic of China.
Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, People's Republic of China.
Sci Rep. 2020 Oct 29;10(1):18587. doi: 10.1038/s41598-020-75783-2.
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.
高迁移率族蛋白 B1(HMGB1)蛋白与多种癌症的发生和增殖有关。根据其功能,HMGB1 在细胞核和细胞质之间穿梭,协助核小体稳定和基因转录,或定位于细胞膜以促进细胞生长。在结直肠癌(CRC)中,这些不同亚细胞位置的临床病理和预后意义及其相关性尚不清楚。我们发现 CRC 和结直肠腺瘤组织样本中核 HMGB1 表达率明显高于正常结直肠组织(分别为 84.0%和 92.6%),而 CRC 组织中细胞质 HMGB1 阳性表达率明显高于结直肠腺瘤(分别为 25.2%和 11.8%)和正常结直肠组织(0.0%)。细胞质 HMGB1 阳性表达与高级别 CRC、预后不良相关,且与 CRC 组织标本中强阳性核 HMGB1 表达呈负相关(r=−0.377,P=0.000)。核 HMGB1 表达强阳性的 CRC 患者的生存预后优于其他 CRC 患者。防止 HMGB1 的核浆易位可能是 CRC 管理的一种新策略。