肺癌肿瘤标志物在多肌炎/皮肌炎相关间质性肺炎中的临床意义  

Clinical significance of tumor markers of lung cancer in interstitial lung disease complicated with polymyositis/dermatomyositis

作　　者：桂贤华[1] 丁晶晶[1] 黄妹[1] 张英为[1] 曹敏[1] 曹孟淑[1] 邱玉英[1] 苗立云[1] 代静泓[1] 蔡后荣[1] 肖永龙[1] Gui Xianhua;Ding Jingjing;Huang Mei;Zhang Yingwei;Cao Min;Cao Mengshu;Qiu Yuying;Miao Liyun;Dai Jinghong;Cai Hourong;Xiao Yonglong(Department of Respiratory and Critical Care Medicine,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院呼吸与危重症医学科,南京210008

出　　处：《国际呼吸杂志》2022年第16期1230-1236,共7页International Journal of Respiration

基　　金：国家自然科学基金(82070064)。

摘　　要：目的探讨肺癌肿瘤相关标志物与多肌炎/皮肌炎(PM/DM)并发间质性肺炎(ILD)的关系,寻找与PM/DM快速进展型间质性肺炎(RPILD)相关的血清标志物。方法本研究为病例对照研究。采用非随机抽样法,选取2016年2月至2019年2月经南京大学医学院附属鼓楼医院确诊为PM/DM合并ILD患者171例,RPILD患者28例,非快速进展型间质性肺炎(Non-RPILD)143例。收集研究对象的临床资料、肺癌相关标志物、炎症指标、肺功能指标等。比较PM/DM相关ILD两种不同表型患者之间的临床及肺癌肿瘤标志物的水平差异。Logistic回归分析获得与RPILD发生相关的变量。通过受试者工作特征(ROC)曲线分析单因素或多因素联合用于区分两种表型的临床意义。组间比较用独立Mann-whitneyU检验,χ2检验。结果与Non-RPILD组相比,RPILD组抗黑色素瘤分化相关基因5(MDA5)抗体阳性率[93%(26/28)比33%(47/143)]高(χ2=19.07,P<0.001);肺癌相关肿瘤标志物:CEA[7.1μg/L(2.6,12.9)μg/L比1.9μg/L(0.9,3.6)μg/L]水平增高(Z=4.06,P<0.001);CYFRA21-1[8.4μg/L(5.6,16.0)μg/L比4.4μg/L(3.0,7.5)μg/L]水平增高(Z=3.66,P<0.001);NSE[25.6μg/L(15.9,28.4)μg/L比16.4μg/L(13.9,20.8)μg/L]水平增高(Z=3.66,P<0.001);炎症指标:乳酸脱氢酶(LDH)[455.0 U/L(352.8,602.8)U/L比287.0 U/L(237.0,386.0)U/L]水平增高(Z=4.65,P<0.001);C反应蛋白(CRP)[20.4 mg/L(8.7,44.9)mg/L比6.1 mg/L(3.2,19.7)mg/L]水平增高(Z=4.06,P<0.001);而CD3^(+)CD4^(+)T淋巴细胞比例[18.9%(10.5%,28.1%)比39.5%(24.5%,59.8%)]水平降低(Z=4.80,P<0.001);氧合指数[187.5 mmHg(101.3,215.0)mmHg比333.0 mmHg(258.0,400.0)mmHg](1 mmHg=0.133 kPa)水平降低(Z=5.79,P<0.001)。抗MDA5抗体、血清CRP、CEA、NSE、CYFRA21-1水平与PM/DM并发RPILD有明显相关性。血清CYFRA21-1联合抗MDA5抗体诊断PM/DM-RPILD的价值最高,敏感度和特异度分别为92.3%和79.6%,曲线下面积达0.88(P<0.001)。结论在PM/DM合并ILD患者中,肺癌相关标志物血清水平升高与PM/DM合并RPILD有关Objective To explore the relationship between lung cancer tumor-related markers and polymyositis/dermatomyositis(PM/DM)complicated with interstitial lung disease(ILD),so as to discover the specific serum markers related to PM/DM rapid progress interstitial lung disease(RPILD).Methods This was a case-control study.A total of 171 adult PM/DM-ILD patients including 28 cases of RPILD and 143 cases of non-RPILD were admitted to the Affiliated Drum Tower Hospital of Nanjing University Medical School between February 2016 and February 2019.The clinical characteristics,serum levels of different lung cancer tumor markers,inflammation indicators,lung function indicators,etc.of each research subject were obtained from the patients′medical files on admission and during follow-up telephone calls.The differences in clinical characteristics and lung cancer tumor marker levels were compared between RPILD and Non-RPILD.Through logistic regression analysis,we obtained the variables related to the occurrence of RPILD.The receiver operating characteristic(ROC)was used to analyze the sensitivity and specificity of different variables related to RPILD.The independent Mann-whitney U test andχ2 test were used for comparison between groups.Results The positive rate of anti-melanoma differentiation-associated gene 5(MDA5)antibody was higher in RPILD patients[93%(26/28)vs 33%(47/143),P<0.001].Compared with PM/DM Non-RPILD patients,PM/DM RPILD patients had elevated levels of CEA[7.1μg/L(2.6,12.9)μg/L vs 1.9μg/L(0.9,3.6)μg/L,Z=4.06,P<0.001],CYFRA21-1[8.4μg/L(5.6,16.0)μg/L vs 4.4μg/L(3.0,7.5)μg/L,Z=3.66,P<0.001],NSE[25.6μg/L(15.9,28.4)μg/L vs 16.4μg/L(13.9,20.8)μg/L,Z=3.66,P<0.001],LDH[455.0 U/L(352.8,602.8)U/L vs 287.0 U/L(237.0,386.0)U/L,Z=4.65,P<0.001]and CRP[20.4 mg/L(8.7,44.9)mg/L vs 6.1 mg/L(3.2,19.7)mg/L,Z=4.06,P<0.001],peripheral blood lymphocyte subset analysis demonstrated that the proportion of CD3^(+)CD4^(+)T cells[18.9%(10.5%,28.1%]vs 39.5%(24.5%,59.8%),Z=4.80,P<0.001]and the oxygenation index[187.5 mmHg(101.3,215.

关 键 词：肺疾病 间质性 癌胚抗原 多肌炎/皮肌炎 神经元特异性烯醇化酶 细胞角蛋白19片段 

分 类 号：R593.26[医药卫生—内科学] R563.13[医药卫生—临床医学]