Peripheral blood non-canonical small non-coding RNAs as novel biomarkers in lung cancer
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Peripheral blood non-canonical small noncoding RNAs as novel biomarkers in lung cancer Wanjun Gu1*†, Junchao Shi2†, Hui Liu3†, Xudong Zhang2†, Jin J. Zhou4, Musheng Li5, Dandan Zhou5, Rui Li3, Jingzhu Lv3, Guoxia Wen1, Shanshan Zhu1, Ting Qi1, Wei Li6, Xiaojing Wang6, Zhaohua Wang7ˆ, Hua Zhu8, Changcheng Zhou2, Kenneth S. Knox9, Ting Wang9, Qi Chen2*, Zhongqing Qian3* and Tong Zhou5*
Abstract One unmet challenge in lung cancer diagnosis is to accurately differentiate lung cancer from other lung diseases with similar clinical symptoms and radiological features, such as pulmonary tuberculosis (TB). To identify reliable biomarkers for lung cancer screening, we leverage the recently discovered non-canonical small non-coding RNAs (i.e., tRNA-derived small RNAs [tsRNAs], rRNA-derived small RNAs [rsRNAs], and YRNA-derived small RNAs [ysRNAs]) in human peripheral blood mononuclear cells and develop a molecular signature composed of distinct ts/rs/ysRNAs (TRY-RNA). Our TRY-RNA signature precisely discriminates between control, lung cancer, and pulmonary TB subjects in both the discovery and validation cohorts and outperforms microRNA-based biomarkers, which bears the diagnostic potential for lung cancer screening. Keywords: Lung cancer, Tuberculosis, tsRNA, rsRNA, ysRNA One unmet challenge in current lung cancer diagnosis is to accurately differentiate lung cancer from other lung diseases with similar clinical symptoms and radiological features. Imaging-based screening methods, such as low-dose computed topography (LDCT), could sometimes be false positives, as indeterminate pulmonary nodules may also be caused by other lung diseases such as pulmonary * Correspondence: [email protected]; [email protected]; [email protected]; [email protected] ˆZhaohua Wang is deceased. 1 State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, 2 Sipailou, Nanjing 210096, Jiangsu, China 2 Division of Biomedical Sciences, School of Medicine, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA 3 Anhui Province Key Laboratory of Immunology in Chronic Diseases, Anhui Key Laboratory of Infection and Immunity, Department of Laboratory Medicine, Bengbu Medical College, 2600 Donghaidadao, Bengbu 233003, Anhui, China 5 Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, 1664 North Virginia Street, Reno, Nevada 89557, USA Full list of author information is available at the end of the article
tuberculosis (TB) [1], which is especially concerning for clinical practice in TB-endemic countries/regions. Therefore, additional noninvasive diagnostic procedures are muchneeded to avoid a misdiagnosis in patients with lung cancer mimicking pulmonary TB, or vice versa. Here, we aim to develop a peripheral blood mononuclear cell (PBMC)-based molecular signature to differentiate lung cancer patients from healthy controls and pulmonary TB patients by harnessing the novel small non-coding RNAs
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