Zhang Wenjia, An Fangmei, Xia Min, Zhan Qiang, Tian Wenying, Jiao Yang
Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing, Medical University, Wuxi, Jiangsu.
School of Radiation Medicine and Protection and Collaborative Innovation Center, Radiation Medicine of Jiangsu Higher Education Institutions, Medical School of Soochow University, Suzhou, China.
Medicine (Baltimore). 2019 Jan;98(3):e14069. doi: 10.1097/MD.0000000000014069.
The aim of this study was to investigate the relationship between high-mobility group box 1 (HMGB1) and colorectal cancer (CRC).In this prospective study, patients with CRC undergoing primary surgery and healthy subjects (control group) were enrolled from July 2013 to December 2014. The serum HMGB1 concentration and HMGB1 mRNA expression were determined using enzyme-linked immunosorbent assay reverse transcription-polymerase chain reaction, respectively. Immunohistochemical analysis was performed to determine HMGB1, pERK, and c-inhibitor of apoptosis protein 2 (c-IAP2) protein expression levels in the cancer tissues.A total 144 patients with CRC and 50 healthy subjects underwent serum HMGB1 testing. Resected specimens of 50 patients were used for HMGB1 mRNA and protein expression analyses. Mean serum HMGB1 level in the patients with CRC was higher than that of the control group (8.42 μg/L vs 1.79 μg/L, P < .05). Mean serum HMGB1 level in the patients with CRC with distant metastasis was significantly higher than that of the controls (13.32 μg/L vs 7.37 μg/L, P < .05). The HMGB1 mRNA and protein expression levels in the CRC tissues were significantly higher than those in the adjacent normal mucosa. HMGB1 protein expression positively correlated with the lymph node metastasis. There were positive correlations between HMGB1 and c-IAP2 (r = 0.457, P < .05), HMGB1 and pERK (r = 0.461, P < .05), as well as pERK and c-IAP2 (r = 0.399, P < .05).HMGB1 expression in CRC correlates with distant and lymph node metastasis. It may inhibit apoptosis by inducing activation of pERK and c-IAP2.
本研究旨在探讨高迁移率族蛋白B1（HMGB1）与结直肠癌（CRC）之间的关系。在这项前瞻性研究中，2013年7月至2014年12月纳入了接受初次手术的CRC患者和健康受试者（对照组）。分别采用酶联免疫吸附测定和逆转录-聚合酶链反应测定血清HMGB1浓度和HMGB1 mRNA表达。进行免疫组织化学分析以确定癌组织中HMGB1、磷酸化细胞外信号调节激酶（pERK）和凋亡抑制蛋白2（c-IAP2）的蛋白表达水平。共有144例CRC患者和50例健康受试者接受了血清HMGB1检测。50例患者的切除标本用于HMGB1 mRNA和蛋白表达分析。CRC患者的平均血清HMGB1水平高于对照组（8.42μg/L对1.79μg/L，P<0.05）。有远处转移的CRC患者的平均血清HMGB1水平显著高于对照组（13.32μg/L对7.37μg/L，P<0.05）。CRC组织中HMGB1 mRNA和蛋白表达水平显著高于相邻正常黏膜。HMGB1蛋白表达与淋巴结转移呈正相关。HMGB1与c-IAP2之间（r=0.457，P<0.05）、HMGB1与pERK之间（r=0.461，P<0.05）以及pERK与c-IAP2之间（r=0.399，P<0.05）均呈正相关。CRC中HMGB1的表达与远处和淋巴结转移相关。它可能通过诱导pERK和c-IAP2的激活来抑制细胞凋亡。
