Rui Zheng1,2, Jiayuan Liang1,2, Jiafei Lu1,2, Shuwei Li1,2, Gang Zhang1,2,3, Xiaowei Wang1,2, Mengting Liu1,2, Weizhi Wang4, Haiyan Chu1,2, Guoquan Tao5, Qinghong Zhao6, Meilin Wang1,2,7, Mulong Du8,9, Fulin Qiang10, Zhengdong Zhang11,12,13. 1. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. 2. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. 3. Department of Neurology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, China. 4. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 5. Department of General Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China. 6. Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. 7. Department of Environmental Genomics, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China. 8. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. drdumulong@njmu.edu.cn. 9. Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China. drdumulong@njmu.edu.cn. 10. Department of Core Laboratory, Nantong Tumor Hospital, Nantong, China. qiangfulin@126.com. 11. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. drzdzhang@gmail.com. 12. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. drzdzhang@gmail.com. 13. Department of Environmental Genomics, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China. drzdzhang@gmail.com.
Abstract
BACKGROUND: Although long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear. METHODS: To screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes. RESULTS: A total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, and CTDHUT) were significantly higher in GC plasma as compared with healthy controls (P < 0.05), and the combined area under curve of these lncRNAs was 0.818 (95% CI 0.772-0.864). Moreover, these lncRNAs were stable and detectable in human plasma, and also enriched in extracellular fluid. The expression levels of all three lncRNAs dropped significantly on day 10 after radical surgery compared with preoperative levels (P < 0.05). Also, lncRNA FAM49B-AS significantly promoted GC cell viability and invasion. CONCLUSIONS: Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.
BACKGROUND: Although long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear. METHODS: To screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes. RESULTS: A total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, and CTDHUT) were significantly higher in GC plasma as compared with healthy controls (P < 0.05), and the combined area under curve of these lncRNAs was 0.818 (95% CI 0.772-0.864). Moreover, these lncRNAs were stable and detectable in human plasma, and also enriched in extracellular fluid. The expression levels of all three lncRNAs dropped significantly on day 10 after radical surgery compared with preoperative levels (P < 0.05). Also, lncRNA FAM49B-AS significantly promoted GC cell viability and invasion. CONCLUSIONS: Plasma lncRNA FAM49B-AS, GUSBP11 and CTDHUT have a strong potential to serve as noninvasive biomarkers for GC diagnosis.