Objective To study the role of serum growth differentiation factor-15(GDF-15) as a diagnostic marker and a chemotherapy response predictor in lung cancer so as to provide a clinical reference.Methods The participants met the inclusion criteria of this study were all selected from the First Affiliated Hospital of Anhui Medical University,included 88 inpatients with lung cancer(lung cancer group) and 31 inpatients with pneumonia(pneumonia group) treated in Department of Respiratory Medicine,and 41 healthy controls(normal control group) undergoing health examination in Medical Examination Center,between December 2015 and August 2016.The serum GDF-15 level was measured in both lung cancer and pneumonia groups on the day of admission and in the normal control group on the first day of undergoing health examination.We collected the lung cancer group′s data of smoking history,diabetes history,measurement results of laboratory markers such as hemoglobin(HGB),prealbumin(PA) and lactate dehydrogenase(LDH) and pathological features(T staging,N staging,clinical staging and pathological types of lung cancer),pneumonia and lung cancer groups′ data of measurement results of serum GDF-15,carcinoembryonic antigen(CEA),neuronspecific enolase(NSE) and cytokeratin 19 fragment(CYFRA21-1) levels.ROC curve of serum GDF-15,CEA,NSE and CYFRA21-1 levels for the diagnosis of lung cancer was evaluated,respectively.In lung cancer patients who completed two consecutive cycles of chemotherapy,chemotherapy response was evaluated and serum GDF-15 level was measured for assessing the chemotherapy response.Results Normal control group had lower serum GDF-15 level than pneumonia group and lung cancer group(P<0.05).Lung cancer group had higher serum GDF-15 level than the pneumonia group(P<0.05).In the lung cancer group,patients with BMI ≥24 kg/m2 had higher serum GDF-15 levels than those with BMI <24 kg/m2(P<0.05);patients with diabetes had higher serum GDF-15 levels than those without(P<0.05),patients with lower serum HGB levels had higher serum GDF-15 levels than those with normal serum HGB levels(P<0.05);Stage T1-2 lung cancer patients had lower serum GDF-15 levels than stage T3-4 lung cancer patients(P<0.05).For the diagnosis of lung cancer,the serum GDF-15 level′s cut off value,sensitivity,specificity,area under the ROC curve(AUC) value,Youden′s index were 1 199.05 ng/L,78.2%,71.0%,0.851〔95%CI(0.774,0.910)〕 and 0.492,respectively.Serum GDF-15 had higher AUC value than serum CEA〔0.630,95%CI(0.537,0.717)〕,NSE〔0.720,95%CI(0.631,0.799)〕 and CYFRA21-1〔0.654,95%CI(0.561,0.739)〕 for the prediction of lung cancer(P<0.05).In the 64 lung cancer cases completing two consecutive cycles of chemotherapy,the condition was partially relieved in 11 cases,stable in 33 cases,and progressive in 20 cases;There was significant difference in serum GDF-15,CEA levels in lung cancer group with different therapeutic effects after chemotherapy(P <0.05).There was no significant difference in serum NSE and CYFRA21-1 levels in lung cancer group with different therapeutic effects after chemotherapy(P>0.05).Conclusion Serum GDF-15 can be used as a diagnostic marker,and a promising new chemotherapy response predictor in lung cancer.%目的 探讨血清生长分化因子15(GDF-15)水平在肺癌的诊断及化疗疗效评估中的价值,为临床提供参考.方法 选取2015年12月-2016年8月就诊于安徽医科大学第一附属医院呼吸内科符合纳入标准的肺癌患者88例、肺炎患者31例以及来自本院体检中心的健康者41例,分别作为肺癌组、肺炎组和正常对照组.检测患者入院时、健康者体检第1天时血清GDF-15水平,同时收集肺癌组患者吸烟情况、合并糖尿病情况、实验室检查指标〔血红蛋白(HGB)、前清蛋白(PA)、乳酸脱氢酶(LDH)〕、病理学特征(T分期、N分期、临床分期、病理类型);收集肺炎组、肺癌组患者血清GDF-15、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)水平,绘制其诊断肺癌的受试者工作特征(ROC)曲线.观察连续2个化疗周期后肺癌组患者的临床疗效,并检测其血清GDF-15水平,分析血清GDF-15水平评估不同化疗疗效的价值.结果 肺炎组、肺癌组血清GDF-15水平高于正常对照组(P<0.05);肺癌组血清GDF-15水平高于肺炎组(P<0.05).体质指数≥24 kg/m2肺癌组患者血清GDF-15水平高于体质指数<24 kg/m2者,合并糖尿病肺癌组患者血清GDF-15水平高于无糖尿病者,血清HGB水平低于正常的肺癌组患者血清GDF-15水平高于血清HGB水平正常者(P<0.05).T1~2期肺癌组患者血清GDF-15水平低于T3~4期者(P<0.05).血清GDF-15水平诊断肺癌的截断值为1 199.05 ng/L,其灵敏度为78.2%,特异度为71.0%,ROC曲线下面积(AUC)为0.851〔95%CI(0.774,0.910)〕,约登指数为0.492.血清CEA、NSE、CYFRA21-1水平诊断肺癌的AUC分别为0.630〔95%CI(0.537,0.717)〕、0.720〔95%CI(0.631,0.799)〕和0.654〔95%CI(0.561,0.739)〕.血清GDF-15水平诊断肺癌的AUC大于血清CEA、NSE、CYFRA21-1水平诊断肺癌的AUC(P<0.05).肺癌组64例患者完成连续2个化疗周期,其中部分缓解11例、疾病稳定33例、疾病进展20例.化疗后不同疗效肺癌组患者血清GDF-15、CEA水平比较,差异有统计学意义(P<0.05);化疗后不同疗效肺癌组患者血清NSE、CYFRA21-1水平比较,差异无统计学意义(P>0.05).结论 血清GDF-15水平可作为筛查肺癌的血清标志物,且有望成为化疗疗效评价的新指标.
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