Li Ning, Holden Van K, Deepak Janaki, Todd Nevins W, Jiang Feng
Departments of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Departments of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Transl Oncol. 2021 Feb;14(2):100991. doi: 10.1016/j.tranon.2020.100991. Epub 2020 Dec 14.
Tumor antigens (TAs) can initiate host immune responses and produce TA-associated autoantibody (TAAbs), potential cancer biomarkers. Sputum is directly generated from the upper and lower airways, and thus can be used as a surrogate sample for the diagnosis of lung cancer based on molecular analysis. To develop sputum TAAb biomarkers for the early detection of lung cancer, the leading cause of cancer death, we probed a protein microarray containing more than 9,000 antigens with sputum supernatants of a discovery set of 30 lung cancer patients and 30 cancer-free smokers. Twenty-eight TAs with higher reactivity in sputum of lung cancer cases vs. controls were identified. The diagnostic significance of TAAbs against the TAs was determined by enzyme-linked immunosorbent assays (ELISAs) in sputum of the discovery set and additional 166 lung cancer patients and 213 cancer-free smokers (validation set). Three sputum TAAbs against DDX6, ENO1, and 14-3-3ζ were developed as a biomarker panel with 81% sensitivity and 83% specificity for diagnosis of lung cancer, regardless of stages, locations, and histological types of lung tumors. This study provides the first evidence that sputum TAAbs could be used as biomarkers for the early detection of lung cancer.
肿瘤抗原（TAs）可引发宿主免疫反应并产生TA相关自身抗体（TAAbs），这是潜在的癌症生物标志物。痰液直接产生于上、下呼吸道，因此可作为基于分子分析诊断肺癌的替代样本。为了开发用于肺癌早期检测的痰液TAAb生物标志物（肺癌是癌症死亡的主要原因），我们用30例肺癌患者和30例无癌吸烟者的发现集痰液上清液检测了一个包含9000多种抗原的蛋白质微阵列。在肺癌病例组与对照组的痰液中，鉴定出28种反应性更高的TA。通过酶联免疫吸附测定（ELISA）在发现集以及另外166例肺癌患者和213例无癌吸烟者（验证集）的痰液中确定了针对这些TA的TAAb的诊断意义。针对DDX6、ENO1和14-3-3ζ的三种痰液TAAb被开发为一个生物标志物组合，对肺癌诊断的敏感性为81%，特异性为83%，无论肺癌的分期、位置和组织学类型如何。本研究提供了首个证据，表明痰液TAAb可作为肺癌早期检测的生物标志物。
