Yuchen Li1,2, Jingjing Zhao1,2, Shulin Yu3, Zhen Wang1, Xigan He4, Yonghui Su5, Tianan Guo6, Haoyue Sheng7, Jie Chen8, Qiupeng Zheng1, Yan Li1, Weijie Guo1, Xiaohong Cai9, Guohai Shi7, Jiong Wu5, Lu Wang4, Peng Wang10, Xianghuo He11,2, Shenglin Huang11,2. 1. Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. 4. Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 5. Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China. 6. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 7. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China. 8. Department of Gastric Cancer and Soft Tissue Sarcomas, Fudan University Shanghai Cancer Center, Shanghai, China. 9. Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China. 10. Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; wangp413@163.com xhhe@fudan.edu.cn slhuang@fudan.edu.cn. 11. Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China; wangp413@163.com xhhe@fudan.edu.cn slhuang@fudan.edu.cn.
Abstract
BACKGROUND: Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS: We presented an optimized strategy for exLR sequencing (exLR-seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types), and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS: More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR-seq sample from 1-2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) = 0.9527; 95% CI, 0.9170-0.9883], validation cohort (AUC = 0.9825; 95% CI, 0.9606-1), and testing cohort (AUC = 0.9627; 95% CI, 0.9263-0.9991). CONCLUSIONS: In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.
BACKGROUND: Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS: We presented an optimized strategy for exLR sequencing (exLR-seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types), and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS: More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR-seq sample from 1-2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) = 0.9527; 95% CI, 0.9170-0.9883], validation cohort (AUC = 0.9825; 95% CI, 0.9606-1), and testing cohort (AUC = 0.9627; 95% CI, 0.9263-0.9991). CONCLUSIONS: In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.
Authors: Ryan Charles Pink; Ellie-May Beaman; Priya Samuel; Susan Ann Brooks; David Raul Francisco Carter Journal: Br J Cancer Date: 2022-01-10 Impact factor: 7.640
Authors: Mohieddin Barzegar; Mehdi Allahbakhshian Farsani; Mohammad Rafiee; Vahid Amiri; Sayeh Parkhihdeh; Fariba Rad; Mohammad Hossein Mohammadi Journal: Ann Hematol Date: 2021-07-08 Impact factor: 3.673
Authors: Yining Xu; Teng Yao; Haonan Ni; Rujie Zheng; Kangmao Huang; Yizhen Huang; Jun Gao; Di Qiao; Shuying Shen; Jianjun Ma Journal: Front Cell Dev Biol Date: 2021-04-22