血清内皮生长因子A、可溶性尿激酶型纤溶酶原激活物受体与肝细胞癌经动脉化疗栓塞治疗反应及预后的关系

Relationship of Serum Vascular Endothelial Growth Factor A and Soluble Urokinase Plasminogen Activator Receptor with Response of Transcatheter Arterial Chemoembolization and Prognosis in Patients with Hepatocellular Carcinoma

[目的]探讨肝细胞癌(HCC)患者血清血管内皮生长因子A(VEGF-A)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)水平与经动脉化疗栓塞术(TACE)治疗反应及预后的相关性。[方法] 2016年1月至2018年12月共纳入在海南省肿瘤医院接受TACE一线治疗100例HCC患者作为研究对象(HCC组),依据改良的实体瘤反应评价标准,分为客观缓解组和非客观缓解组。另外收集30位健康人的血清样本作为健康对照组。HCC患者于TACE治疗前1~2 d取血清标本。随机选取25例患者基线血清标本,采用多重细胞因子定量抗体芯片分析血清样本中血管生成相关因子含量。采用酶联免疫吸附测定法检测受试者血清VEGF-A、suPAR水平。随访至2022年2月28日。[结果]经多重细胞因子芯片分析,客观缓解患者和非客观缓解患者基线血清VEGF-A(变化倍数为0.69,P=0.097)、suPAR(变化倍数为0.82,P=0.014)水平存在统计学差异。HCC组患者基线血清VEGF-A、suPAR水平均高于健康对照组(P<0.001)。血清VEGF-A和suPAR在区分HCC组和健康对照组时的ROC曲线下面积分别为0.931(95%CI:0.876~0.987)和0.855(95%CI:0.785~0.926)。非客观缓解组患者基线血清suPAR水平显著性高于客观缓解组(P<0.001),且基线血清suPAR是影响HCC患者TACE治疗反应的独立预测因素(P<0.05)。基线血清suPAR高水平患者总生存期明显缩短(12.5个月vs 32.2个月,P<0.001)。[结论] HCC患者血清VEGF-A、suPAR水平普遍升高,且血清suPAR是TACE治疗反应的独立影响因素。基线血清suPAR水平越高则预示着HCC患者TACE治疗反应和预后不良。

[Objective] To investigate the relationship of serum vascular endothelial growth factor A(VEGF-A) and soluble urokinase plasminogen activator receptor(suPAR) with the response of transcatheter arterial chemoembolization(TACE) and prognosis of patients with hepatocellular carcinoma(HCC). [Methods] A total of 100 HCC patients receiving first-line TACE in Hainan Cancer Hospital from January 2016to December 2018 were included in the study and followed up until the end of February 2022. According to the modified solid tumor response evaluation criteria, the patients were divided into objective remission group and non-objective remission group. Serum samples were collected from HCC patients 1~2 d before TACE and also collected from 30 healthy subjects as controls. The serum VEGF-A and suPAR levels were measured by enzyme-linked immunosorbent assay(ELISA) in all subjects. The levels of angiogenic related factors in serum samples from 25 patients were analyzed by Multiplex Quantibody Human Angiogenesis Array 1000. [Results] The baseline serum VEGF-A and suPAR levels in HCC patients were higher than those in healthy controls(P<0.001). The area under the receiver operating characteristic curve(AUC) of serum VEGF-A and suPAR in differentiating HCC from healthy controls were 0.931(95%CI: 0.876~0.987)and 0.855(95%CI: 0.785~0.926), respectively. The serum suPAR level in non-objective remission group was significantly higher than that in objective remission group(P<0.001), and it was an independent predictor of the response to TACE in HCC patients(P <0.05). Kaplan-Meier survival curves showed that the overall survival time was significantly shorter in the high su PAR group(12.5 months vs. 32.2 months, P<0.001). [Conclusion] The serum levels of VEGF-A and su PAR are higher in HCC patients. su PAR would be an independent factor influencing the response to TACE and the higher baseline serum Su PAR level predicts poor TACE response and prognosis in HCC patients.