血管内皮生长因子在黑色素瘤疗效监测和预后判断中的价值

Role of vascular endothelial growth factor in monitoring treatment outcome and evaluating the prognosis of patients with advanced melanoma

目的 探讨血清血管内皮生长因子(VEGF)在黑色素瘤疗效监测和预后评估中的应用价值。方法选取黑色素瘤患者49例(黑色素瘤组)、健康体检者182名(正常对照组),检测所有对象血清VEGF水平。收集所有患者的临床资料(性别、年龄、临床分期、化疗方案、疗效评价、肿瘤发病部位、是否发生溃疡和是否有肿瘤驱动基因突变)。对所有患者随访24个月,记录疾病无进展生存期(PFS)和总生存期(OS)。采用Kaplan-Meier生存曲线分析不同VEGF水平患者PFS和OS的差异。采用Cox回归分析评估黑色素瘤患者PFS和OS的影响因素。结果 黑色素瘤组VEGF阳性率(48.98%)显著高于正常对照组(3.85%)(P<0.001)。根据血清VEGF水平是否升高将黑色素瘤患者分为VEGF正常组(25例)和VEGF升高组(24例)。血清VEGF水平升高与黑色素瘤患者疗效有关(P=0.001),与患者性别、年龄、肿瘤发病部位、是否发生溃疡、临床分期及是否有肿瘤驱动基因突变均无关(P>0.05)。VEGF升高组PFS(3个月)显著短于VEGF正常组(9个月)(P=0.02);OS稍短于VEGF正常组,但差异无统计学意义(P>0.05)。血清VEGF水平升高和临床分期Ⅳ期是黑色素瘤患者出现疾病进展的危险因素[风险比(HR)分别为2.55、4.64,95%可信区间(CI)分别为1.07~6.10、1.40~15.43],临床分期Ⅳ期是黑色素瘤患者OS缩短的危险因素(HR=14.52,95%CI为2.67~79.08)。结论 血清VEGF在黑色素瘤疗效监测和预后评估方面具有潜在的临床应用价值。

Objective To investigate the application role of serum vascular endothelial growth factor(VEGF)in monitoring treatment outcome and predicting the prognosis of patients with melanoma. Methods A total of 182healthy subjects and 49 melanoma patients were enrolled. Serum samples were collected for analyzing the levels of serum VEGF. Clinical data,including sex,age,clinical stage,chemotherapy,treatment outcome,primary site,ulcer,mutations of driver genes,were collected. All the patients were followed up for 24 months,and the progression-free survival time(PFS) and overall survival time(OS) were recorded. The PFS and OS were analyzed by Kaplan-Meier survival curve. The factors for PFS and OS in melanoma patients were analyzed by Cox regression analysis. Results Melanoma patients(48.98%)have a higher VEGF positive rate than healthy subjects(3.85%)(P<0.001). The melanoma patients were classified into 2 groups,VEGF normal group(25 cases) and VEGF increased group(24 cases). Increased VEGF level was related to poor treatment outcome(P=0.001),but it was not related to sex,age,tumor location,ulcer,clinical stage or driver gene mutation(P>0.05). For patients with increased VEGF level(3 months),PFS was shorter than that of patients with normal VEGF(9 months)(P=0.02),and OS was shorter without statistical significance(P>0.05). Patients with increased VEGF and advanced stage(Ⅳ)had increased risk of disease progression [hazard ratio(HR)=2.55 and 4.64,95% confidence intervals(CI) were 1.07-6.10 and 1.40-15.43]. Advanced stage(Ⅳ) was a risk factor for short OS in melanoma patients(HR=14.52,95%CI 2.67-79.08). Conclusions VEGF in serum may be a circulating biomarker to predict treatment outcome in patients with advanced melanoma.