食管鳞癌患者血清血红素氧合酶-1和鳞状细胞癌抗原水平与临床病理特征及预后的关系

Relationships of serum heme oxygenase-1and squamous cell carcinoma antigen with clinicopathological parameters and prognosis of esophageal squamous cell carcinoma

目的观察不同临床病理特征食管鳞癌患者血清血红素氧合酶-1(heme oxygenase-1,HO-1)、鳞状细胞癌抗原(squamous cell carcinoma antigen,SCCA)水平变化,探讨HO-1、SCCA与食管鳞癌患者预后的关系。方法食管鳞癌患者93例为食管鳞癌组,同期体检健康者72例为对照组,采用ELISA法检测2组血清HO-1、SCCA水平。比较食管鳞癌组与对照组及不同临床病理特征食管鳞癌患者血清HO-1、SCCA水平。食管鳞癌患者根据病情程度采用内镜治疗、食管癌根治术治疗及放化疗综合治疗,并依据HO-1、SCCA水平分为高水平HO-1(HO-1≥2.43μg/L)组47例和低水平HO-1(HO-1<2.43μg/L)组46例,高水平SCCA(SCCA≥2.76μg/L)组49例和低水平SCCA(SCCA<2.76μg/L)组44例。随访5年,比较食管鳞癌患者高、低水平HO-1组,高、低水平SCCA组5年总生存率,多因素Cox回归分析食管鳞癌患者死亡的危险因素。结果食管鳞癌组血清HO-1[(2.43±0.55)μg/L]、SCCA[(2.76±0.61)μg/L]水平高于对照组[(0.23±0.09)、(0.42±0.13)μg/L](P<0.05)。肿瘤分期Ⅲ期、病理分级低分化者血清HO-1[(2.75±0.64)、(2.57±0.57)μg/L]、SCCA[(3.22±0.71)、(2.93±0.64)μg/L]水平高于肿瘤分期Ⅰ~Ⅱ期[(2.32±0.43)、(2.60±0.52)μg/L]、病理分级高中分化者[(2.30±0.51)、(2.61±0.58)μg/L](P<0.05);不同年龄、性别、肿瘤大小、肿瘤位置及淋巴结有无转移者血清HO-1、SCCA水平比较差异均无统计学意义(P>0.05)。随访至2020年2月,均未失访,高水平HO-1组5年总生存率(10.6%)低于低水平HO-1组(30.4%)(P<0.05),高水平SCCA组5年总生存率(8.2%)低于低水平SCCA组(34.1%)(P<0.05)。肿瘤分期Ⅲ期(OR=3.054,95%CI=1.021~6.141,P=0.004)、病理分级低分化(OR=3.011,95%CI:1.003~5.051,P=0.023)、高血清HO-1水平(OR=2.407,95%CI:1.123~4.989,P=0.022)、高血清SCCA水平(OR=2.025,95%CI:1.003~8.077,P=0.019)是食管鳞癌患者死亡的危险因素。结论食管鳞癌患者血清HO-1及SCCA水平升高,其增高程度与肿瘤分期、病理分级有关,是食管鳞癌患者死亡的危险因素。

Objective To observe the changes of serum heme oxygenase-1(HO-1)and squamous cell carcinoma antigen(SCCA)in patients with different clinicopathological features of esophageal squamous cell carcinoma,and to explore their relationships with the patients'prognosis.Methods The levels of HO-1and SCCA in serum were detected by ELISA in 93patients with esophageal squamous cell carcinoma(carcinoma group)and 72healthy volunteers in the same period(control group),and were compared between two groups and among patients with different clinicopathological features.Endoscopic treatment,radical resection of esophageal cancer and chemoradiotherapy were performed according to the patient's condition.Carcinoma group was redivided into high HO-1group(HO-1≥2.43μg/L,n=47)and low HO-1 group(HO-1<2.43μg/L,n=46),and high SCCA group(SCCA≥2.76μg/L,n=49)and low SCCA group(SCCA<2.76μg/L,n=44).All patients were followed up for 5years,the 5-year overall survival rate was compared between high and low HO-1groups and between high and low SCCA groups.Multivariate Cox regression analysis was used to analyze the risk factors of poor prognosis of patients with esophageal squamous cell carcinoma.Results The serum levels of HO-1and SCCA were higher in carcinoma group((2.43±0.55),(2.76±0.61)μg/L)than those in control group((0.23±0.09),(0.42±0.13)μg/L](P<0.05).The serum HO-1levels((2.75±0.64),(2.57±0.57)μg/L)and SCCA levels((3.22±0.71),(2.93±0.64)μg/L)in patients with tumor stageⅢand poorly differentiated carcinoma were higher than those in patients with tumor stageⅠ-Ⅱ((2.32±0.43),(2.60±0.52)μg/L)and highly/moderately differentiated carcinoma((2.30±0.51),(2.61±0.58)μg/L)(P<0.05).There were no significant differences in the serum HO-1and SCCA levels among patients with different ages,genders,tumor sizes,tumor locations and lymph node metastasis or not(P>0.05).All patients were followed up till February,2020.The 5-year overall survival rate was lower in high HO-1group(10.6%)than that in low HO-1group(30.4%)(P<0.05),and lower in high SCCA group(8.2%)than that in low SCCA group(34.1%)(P<0.05).Tumor stageⅢ(OR=3.054,95%CI:1.021-6.141,P=0.004),poorly differentiated grade(OR=3.011,95%CI:1.003-5.051,P=0.023),high HO-1level(OR=2.407,95%CI:1.123-4.989,P=0.022),and high SCCA level(OR=2.025,95%CI:1.003-8.077,P=0.019)were the risk factor of poor prognosis of patients with esophageal squamous cell carcinoma.Conclusion The levels of serum HO-1and SCCA in patients with esophageal squamous cell carcinoma are elevated,which is correlated with the tumor stage and pathological grade,and the elevated HO-1and SCCA are the risk factors of death of patients with esophageal squamous cell carcinoma.