食管鳞癌患者血清TK1与SCCA表达及其预后价值

目的食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)是我国食管癌的主要病理类型,患者预后较差,5年生存率低,影响ESCC患者对治疗的应答以及预后的相关因素仍不清楚。本研究旨在探讨血清细胞质胸苷激酶1(thymidine kinase 1,TK1)与鳞状细胞癌抗原(squamous cell carcinoma antigen,SCCA)在ESCC同步放化疗前的表达及其预后预测价值。方法选取2013-1-30-2016-10-19淮北矿工总医院收治的96例ESCC患者和100名门诊健康体检者为研究对象,分为ESCC组和对照组。采用酶联免疫吸附实验法(enzyme-linked immunosorbent assay,ELISA)检测入组对象的血清TK1、SCCA的表达,比较2组血清TK1和SCCA表达差异,分析血清TK1和SCCA的表达与ESCC患者临床病理特征的相关性。采用ROC曲线评价血清TK1、SCCA对诊断ESCC价值,分析其与同步放化疗后24个月预后的关系。结果 ESCC组血清TK1表达高于对照组,差异有统计学意义,t=24.665,P<0.05。血清TK1表达量与年龄(t=1.783)、性别(t=0.467)、肿瘤位置(t=1.263)无统计学意义的关联,P>0.05。血清TK1水平病变长度≥5cm高于病变长度<5cm患者,t=3.481,P<0.05;Ⅲ期+Ⅳ期高于Ⅰ+Ⅱ患者,F=6.509,P<0.05;存在淋巴结转移高于无淋巴结转移患者,t=3.613,P<0.05。ESCC组血清SCCA表达高于对照组,差异有统计学意义,t=34.852,P<0.05。血清SCCA表达量与年龄(t=1.473)、性别(t=1.338)、肿瘤位置(t=1.280)无统计学意义的关联,P>0.05。血清SCCA水平病变长度≥5cm高于病变长度<5cm患者,t=3.229,P<0.05;Ⅲ期+Ⅳ期高于Ⅰ+Ⅱ期患者,F=8.513,P<0.05;存在淋巴结转移高于无淋巴结转移患者,t=3.029,P<0.05。血清TK1诊断的临界值为1.97,其对应的灵敏度为75.0%,特异度为85.4%,ROC曲线下面积为0.808,95%CI为0.750~0.896;中位无进展生存期(progression-free survival,PFS)TK1≥1.97pmol/L为9.3个月,<1.97pmol/L为13.6个月,P=0.004;SCCA诊断的临界值为3.54,其对应的灵敏度为83.3%,特异度为66.7%,ROC曲线下面积为0.798,95%CI为0.728~0.869。SCCA≥3.54ng/mL PFS为9.1个月,SCCA<3.54ng/mL为13.6个月,P=0.001。血清TK1、SCCA与患者PFS差异有统计学意义,P<0.05。Cox多因素回归分析显示,临床分期(HR=5.836,95%CI为1.585~21.486)、血清TK1(HR=1.024,95%CI为1.000~1.049)及SCCA(HR=1.879,95%CI为1.183~2.985)水平为影响ESCC患者PFS的独立危险因素,差异有统计学意义,P<0.05,临床分期(HR=1.060,95%CI为1.021~1.100)为影响ESCC患者总生存时间(overall survival,OS)的独立危险因素,差异有统计学意义,P<0.05。结论血清TK1与SCCA在ESCC中的表达受分期、肿瘤病变长度和淋巴结转移影响,二者联合检测对于ESCC具有一定诊断价值,血清TK1与SCCA高表达可以作为评估ESCC患者预后的潜在指标。

Expression of serum TK1 and SCCA in esophageal squamous cell carcinoma patients treated with concomitant chemo-radiotherapy and its predictive value for prognosis

OBJECTIVE Esophageal squamous cell carcinoma(ESCC)is the main pathological type of esophageal cancer in China,the patient’s prognosis is poor,the 5-year survival rate is low,the effect of ESCC patients’ response to treatment and the factors related to prognosis are still unclear.The purpose of this paper was to find suitable molecular markers for clinical prognosis assessment of esophageal squamous cell carcinoma(ESCC),to analyze the expression of serum TK1 and SCCA in ESCC patients treated with concomitant chemo-radiotherapy and its predictive value for prognosis.METHODS Totally 96 ESCC patients(ESCC Group)and 100 health patients(control group)from January 2013 to October 2016 in our hospital were selected as the research subjects.The expression of serum TK1 and SCCA of patients were detected by ELISA method,the differences in the expressions of serum TK1 and SCCA between the two groups were compared.The correlation between the expression of serum TK1 and SCCA as well as the clinicopathologic features of ESCC patients were analyzed,the value of serum TK1 and SCCA in the diagnosis of esophageal squamous cell carcinoma was evaluated by ROC Curve,and the relationship between serum TK1,SCCA and prognosis of 24 months after concomitant chemoradiotherapy were analyzed.RESULTS The expression of serum TK1 in ESCC Group was significantly higher than those in control group,and the difference was statistically significant(t=24.665,P<0.05).There was no significant correlation between serum TK1 expression and age(t=1.783),sex(t=0.467),tumor location(t=1.263),all P>0.05.The level of serum TK1 in patients with lesion length≥5 cm was higher than that in the patients with lesion length<5 cm(t=3.481,P<0.05).The serum TK1 levels in patients withⅢ+Ⅳstage were higher than that in theⅠ+Ⅱstage group(F=6.509,P<0.05);Serum TK1 levels in patients with lymph node metastasis were higher than those without lymph node metastasis group(t=3.613,P<0.05).The expression of serum SCCA in ESCC Group was significantly higher than that in control group,and the difference was statistically significant(t=34.852,P<0.05).There was no significant correlation between serum SCCA expression and age(t=1.473),sex(t=1.338),tumor location(t=1.280),P>0.05.The level of serum SCCA in patients with lesion length ≥5 cm was higher than that in the patients with lesion length<5 cm(t=3.229,P<0.05).The serum SCCA levels in patients with Ⅲ+Ⅳ stage were higher than that in theⅠ+Ⅱstage group(F=8.513,P<0.05);Serum SCCA levels in patients with lymph node metastasis were higher than those without lymph node metastasis group(t=3.029,P<0.05).The critical value of serum TK1 for diagnosis of ESCC was 1.97 pmol/L,the sensitivity was 75%,the specificity was the 85.4%and the AUC was 0.808(95%CI=0.750-0.896).The median PFS of TK1≥1.97 pmol/L and <1.97 pmol/L were 9.3 months and 13.6 months respectively(P=0.004).The critical value of serum SCCA for diagnosis of ESCC was 3.54 ng/ml,the sensitivity was 83.3%,the specificity was the 66.7%and the AUC was 0.798(95%CI=0.728-0.869).The median PFS of the SCCA≥3.54 ng/mL and SCCA <3.54 ng/mL were 9.1 months and 13.6 months respectively(P=0.001).The serum TK1 and SCCA had a significant impact on patients’ PFS(P<0.05).The results of Cox’s multi-factor regression analysis showed clinical staging(HR=5.836,95%CI=1.585-21.486),serum TK1 level(HR=1.024,95%CI=1.001-1.049)and serum SCCA level(HR=1.879,95%CI=1.183-2.985)were the independent risk factors of PFS in ESCC patients(P<0.05)and the clinical staging(HR=1.060,95%CI=1.021-1.100)was an independent risk factor affecting OS in ESCC patients(P<0.05).CONCLUSIONS The serum expressions of TK1 and SCCA in the ESCC patients are associated by the clinical stage,the length of tumor lesions and lymph node metastasis.The joint detection of TK1 and SCCA expression can be used as a diagnosis reference in ESCC with high diagnosis value,the higher expression of TK1 and SCCA can be used as potential indexes in prognosis evaluate.