原发性肝癌组织中溴结构域蛋白4的表达及与临床病理特征和预后的关系

Expression of BRD4 and its relationship with clinicopathological characteristics and prognosis in primary hepatic carcinoma

摘要:

目的 探讨原发性肝癌（PHC）组织中溴结构域蛋白4（BRD4）的表达及与患者临床病理特征及预后的关系。方法 选取2015年7月—2018年7月青海省人民医院收治的PHC患者83例作为研究对象，均行手术切除，术后随访3年。采用免疫组织化学法检测BRD4蛋白的表达，对比癌组织、癌旁组织中BRD4蛋白的表达，分析PHC癌组织中BRD4蛋白表达与患者临床病理特征的关系，影响PHC患者预后的因素，癌组织中BRD4蛋白表达与PHC患者预后的关系。结果 PHC患者癌组织中BRD4阳性表达率高于癌旁组织（P <0.05）。有微血管侵犯、肿瘤包膜不完整、临床分期Ⅲ期、低分化癌组织BRD4蛋白阳性表达率较高（P <0.05）。多因素Cox回归分析结果显示，微血管侵犯［R^R=5.379（95% CI：3.487，13.005）］、肿瘤包膜［R^R=5.614（95% CI：3.986，16.115）］、临床分期［R^R=5.312（95% CI：3.307，12.413）］、分化程度［R^R=4.187（95% CI：2.893，10.006）］、BRD4蛋白表达［R^R=5.799（95% CI：4.156，17.235）］是PHC患者复发的独立影响因素（P <0.05）；肿瘤包膜［R^R=3.152（95% CI：2.150，8.795）］、临床分期［R^R=4.998（95% CI：2.695，11.003）］、分化程度［R^R=5.650（95% CI：3.803，17.001）］、BRD4蛋白表达［R^R=5.987（95% CI：4.384，18.828）］是PHC患者生存的独立影响因素（P <0.05）。BRD4蛋白阳性表达患者与阴性表达患者的无病生存率、总生存率比较，差异有统计学意义（P <0.05），BRD4蛋白阴性表达患者的无病生存率、总生存率均高于BRD4蛋白阳性表达患者。结论 PHC患者癌组织中BRD4蛋白表达与临床病理特征及预后有关，BRD4蛋白阳性表达者预后不良风险高。

Abstract:

Objective To explore the expression of bromodomain-containing protein 4 (BRD4) in primary hepatic carcinoma (PHC) tissues and its relationship with clinicopathological characteristics and prognosis of PHC.Methods A total of 83 patients with PHC admitted to the hospital from July 2015 to July 2018 were selected. All patients underwent surgical resection of PHC and were followed up for a median duration of 3 years. Immunohistochemistry was used to detect the expression of BRD4, which was compared between the cancerous and adjacent tissues. The relationship between the expression of BRD4 in the PHC tissues and the clinicopathological characteristics of the patients was analyzed. Factors affecting the prognosis of PHC patients were determined. The relationship between the expression of BRD4 in the PHC tissues and the prognosis of PHC patients was also analyzed.Results The positive rate of BRD4 expression in cancerous tissues of PHC patients was higher than that in adjacent tissues (P < 0.05). The positive rate of BRD4 expression was higher in cancerous tissues with microvascular invasion and incomplete pseudocapsule, and from stage Ⅲ and poorly differentiated tumors (P < 0.05). The multivariable Cox regression analysis showed that microvascular invasion [R^R = 5.379 (95% CI: 3.487, 13.005) ], tumor pseudocapsule [R^R = 5.614 (95% CI: 3.986, 16.115) ], TNM stage [R^R = 5.312 (95% CI: 3.307, 12.413) ], the degree of differentiation [R^R = 4.187 (95% CI: 2.893, 10.006) ] and the positive expression of BRD4 [R^R = 5.799 (95% CI: 4.156, 17.235) ] were independent factors affecting the relapse of PHC patients (P < 0.05). In contrast, tumor pseudocapsule [R^R = 3.152 (95% CI: 2.150, 8.795)], TNM stage [R^R = 4.998 (95% CI: 2.695, 11.003) ], the degree of differentiation [R^R = 5.650 (95% CI: 3.803, 17.001) ] and the positive expression of BRD4 [R^R = 5.987 (95% CI: 4.384, 18.828) ] were independent factors that affected the overall survival of PHC patients (P < 0.05). There were differences in the disease-free survival and the overall survival between the BRD4-positive and the BRD4-negative patients (P < 0.05), and the disease-free survival curve and the overall survival curve of patients with negative expression of BRD4 were better than those of patients with positive expression of BRD4.Conclusions The expression of BRD4 in cancerous tissues of PHC patients is related to the clinicopathological characteristics and prognosis of these patients. Those with positive expression of BRD4 have a high risk of poor prognosis.