高迁移率族蛋白1在胃癌病人血清中的含量及意义

HMGB1 level in serum of patients with gastric cancer and its clinical significance

目的:高迁移率族蛋白1(high mobility group box-1 protein,HMGB1)是一个多功能细胞因子,与细胞移动和肿瘤浸润有关。本研究通过检测胃癌病人血清HMGB1水平,分析其与胃癌临床病理特征的关系,并与肿瘤标志物CA19-9、CEA进行比较,探讨胃癌病人血清中HMGB1的含量及其临床意义。方法:分别采用ELISA法和化学发光免疫法检测160例胃癌病人术前血清HMGB1、CA19-9和CEA含量和52例胃良性疾病病人、60例正常对照者的血清HMGB1含量,123例胃癌病人同时检测根治术后血清HMGB1含量。结果:胃癌病人血清HMGB1水平(13.1±7.6)ng/mL明显高于正常对照组(4.5±2.9)ng/mL(Р<0.001)和胃良性疾病组(5.2±3.4)ng/mL(Р<0.001)。分层分析发现,随着疾病的进展,血清HMGB1水平逐渐升高,TNMⅢ期和Ⅳ期分别与Ⅰ期进行比较,均有显著差异(Р<0.001)。肿瘤浸润浆膜(Р<0.001)、有淋巴结转移(Р<0.001)及肝脏转移者(Р=0.026)的血清HMGB1水平升高更为明显。根治术后血清HMGB1水平(8.5±5.2)ng/mL比术前(12.4±7.6)ng/mL明显降低(Р<0.001)。此外,160例病人血清HMGB1、CA19-9和CEA的阳性率分别为66.2%、14.3%和8.7%,HMGB1阳性率明显高于CA19-9(Р<0.001)和CEA(Р<0.001)。结论:胃癌病人血清HMGB1水平明显高于正常对照组和胃良性疾病组,且血清HMGB1的表达水平与胃癌的浆膜浸润、淋巴结转移及肝脏转移呈正相关,血清HMGB1表达水平可作为反映胃癌生物学行为和术后随访、监测的参考指标。

Objective High mobility group box-1 protein （HMGB1） is a multifanctional cytokine, which is related to cell migration and tumor invasion. We measured serum concentrations of HMGB1 in patients with gastric cancer and compared with various clinicopathological characteristics and tumor markers such as CEA and CA19-9 to evaluate its clinical significance. Methods Pre-operative serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay system in 160 patients with gastric cancer and serum CEA and CA19-9 level were determined by chemiluminescence immunoassay. In 123 patients with curative resection, post-operative serum HMGBI level was also measured. Serum HMGB1 level of 52 patients with benign gastric disease and 80 healthy controls were measured as control. Results Compared with healthy controls and the patients with benign gastric disease, serum levels of HMGB1 were significantly higher in gastric cancer patients （P〈0.001）. Increased serum HMGB1 level was associated with stage progression. Serum HMGB1 was significantly lower in patients with Stage Ⅰthan those in stage Ⅲ and Ⅳ （P〈0.001）. Patients with serosal invasion （P〈0.001）, lymph node metastasis （P〈0.001） and liver metastasis （P=0.026） had significantly higher serum HMGB1 levels. Serum level of HMGB1 decreased in 123 patients with curative resection after operation, P〈 0.001. Serum HMGB1 level elevated in 66.3% of the patients （106/160）. The positive rate was higher than that for serum CA19-9 （14.4%, 23/160） and CEA （8.8%, 14/160）, P〈0.O01. Conclusions Elevation of serum level of HMGB1 in gastric cancer patients and its association with tumor stage and metastasis suggested that serum HMGB1 level might be a useful marker for monitoring tumor progression in gastric cancer.