A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT)

// Xiaobing Wang 1, * , Xiuyi Zhi 2, * , Zhaogang Yang 3, * , Haimei Tian 1 , Yanfen Li 1 , Mo Li 1 , Wenya Zhao 1 , Chao Zhang 1 , Teng Wang 1 , Jing Liu 1 , Di Shen 4 , Cuining Zheng 4 , Dan Zhao 5 , Sheng Yang 6 , Jun Qi 4 , Hongwu Xin 7, 8 , Alexander Stojadinovic 9 , Itzhak Avital 10 , L. James Lee 3 , Jianyu Rao 1 , Wei Zhang 1 1 Tumor Marker Research Center, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 2 Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China 3 NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA 4 Laboratory of Clinical Biochemistry, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 5 Department of Gynecological Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 6 Department of Medicine, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 7 The First Peoples’ Hospital of Jingzhou City, The First Hospital and Clinical Medical School of Yangtze University, Jingzhou, PR China 8 Laboratory of Oncology, Center for Molecular Medicine, Medical School, Yangtze University, Huber, PR China 9 Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA 10 P8-Medicine Ltd, Sussex, DE, USA * These authors contributed equally to this work Correspondence to: Wei Zhang, email: zhangww1954@126.com Keywords: lung cancer, biomarker, early detection, MIC-1, screening Received: February 03, 2017      Accepted: April 14, 2017      Published: April 27, 2017 ABSTRACT Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and mortality rates in high-risk individuals, which was, however, limited by specifically coverage for heavy smokers and high rates of false positivity. Here, we aim to investigate a novel biomarker for early detection of lung cancer, and further extend to concentrate high-risk subjects for increasing specificity and coverage of LDCT. We performed retrospective blinded evaluation of lung cancer and healthy controls in training and validation cohorts. Macrophage inhibitory cytokine 1 (MIC-1) alone and panel were assessed. Our data showed the sensitivity of MIC-1 was 72.2% and 67.1% for lung cancer diagnosis and early diagnosis respectively, at 96.6% specificity, which were significantly higher than Cyfra21-1, NSE CA125, CEA and SCC. At 90% specificity, the panel of MIC-1, Cyfra21-1, CA125 and CEA provided 89.5% sensitivity for early diagnosis of lung cancer, which could be used to concentrate the high-risk subjects for further LDCT screening. We conclude that MIC-1 have great capacity in early lung cancer diagnosis. The algorithmic panel of MIC-1, Cyfra21-1, CA125 and CEA could be used to refine the preselection criteria of high-risk subjects, and thus might facilitate the widespread implementation of LDCT screening.