Dai Liping, Li Jitian, Tsay Jun-Chieh J, Yie Ting-An, Munger John S, Pass Harvey, Rom William N, Tan Eng M, Zhang Jian-Ying
Institute of Medical and Pharmaceutical Sciences & Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China.
Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA.
Oncoimmunology. 2017 Mar 31;6(5):e1310359. doi: 10.1080/2162402X.2017.1310359. eCollection 2017.
Identification of biomarkers for early detection of lung cancer (LC) is important, in turn leading to more effective treatment and reduction of mortality. Serological proteome analysis (SERPA) was used to identify proteins around 34 kD as ECH1 and HNRNPA2B1, which had been recognized by serum autoantibody from 25 LC patients. In the validation study, including 90 sera from LC patients and 89 sera from normal individuals, autoantibody to ECH1 achieved an area under the curve (AUC) of 0.799 with sensitivity of 62.2% and specificity of 95.5% in discriminating LC from normal individuals, and showed negative correlation with tumor size ( = -0.256, = 0.023). Autoantibody to HNRNPA2B1 performed an AUC of 0.874 with sensitivity of 72.2% and specificity of 95.5%, and showed negative correlation with lymph node metastasis ( = -0.279, = 0.012). By using longitudinal preclinical samples, autoantibody to ECH1 showed an AUC of 0.763 with sensitivity of 60.0% and specificity of 89.3% in distinguishing early stage LC from matched normal controls, and elevated autoantibody levels could be detected greater than 2 y before LC diagnosis. ECH1 and HNRNPA2B1 are autoantigens that elicit autoimmune responses in LC and their autoantibody can be the potential biomarkers for the early detection of LC.
鉴定用于肺癌(LC)早期检测的生物标志物很重要,这反过来会带来更有效的治疗并降低死亡率。血清蛋白质组分析(SERPA)被用于鉴定约34kD的蛋白质为ECH1和HNRNPA2B1,它们已被25例LC患者的血清自身抗体识别。在验证研究中,包括90例LC患者的血清和89例正常个体的血清,ECH1自身抗体在区分LC与正常个体时曲线下面积(AUC)为0.799,敏感性为62.2%,特异性为95.5%,并且与肿瘤大小呈负相关(r = -0.256,P = 0.023)。HNRNPA(2)B1自身抗体的AUC为0.874,敏感性为72.2%,特异性为95.5%,并且与淋巴结转移呈负相关(r = -0.279,P = 0.012)。通过使用纵向临床前样本,ECH1自身抗体在区分早期LC与匹配的正常对照时AUC为0.763,敏感性为60.0%,特异性为89.3%,并且在LC诊断前2年多就能检测到自身抗体水平升高。ECH1和HNRNPA2B1是在LC中引发自身免疫反应的自身抗原,它们的自身抗体可能是LC早期检测的潜在生物标志物。