AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (1.9 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Full Length Article | Open Access

Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer

Yi Zuoa,b,1Shaoqiu Chenb,c,1Lingling Yana,1Ling Hua,1Scott Bowlerb,cEmory Zitellob,cGang Huangd( )Youping Dengb( )
Tianyou Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan 430064, PR China
Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA
Molecular Biosciences and Bioengineering Program, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa, Honolulu, HI 96822, USA
Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work.

Show Author Information

Abstract

Liver cancer presents divergent clinical behaviors. There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis, especially since tRNA-derived small RNAs (tsRNA) have rarely been studied. In this study, a random forests (RF) diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation (IV). A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer prognosis. Model performance was evaluated by a receiver operating characteristic curve (ROC curve) and Precision-Recall curve (PR curve). The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve (AUROC) 88% and area under the precision–recall curve (AUPR) 87% in the discovery cohort and 87% and 86% in IV-AUROC and IV-AUPR, respectively. The seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients (Hazard Ratio 2.02, 95% CI 1.36–3.00, P < 0.001), independent of standard clinicopathological prognostic factors. Moreover, the model successfully categorizes patients into high-low risk groups. Diagnostic and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.

References

1

Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Canc. 2015;136(5):E359-E386.

2

McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015;19(2):223-238.

3

Medavaram S, Zhang Y. Emerging therapies in advanced hepatocellular carcinoma. Exp Hematol Oncol. 2018;7(1):17.

4

Tsochatzis E, Meyer T, O'Beirne J, Burroughs AK. Transarterial chemoembolisation is not superior to embolisation alone: the recent European Association for the Study of the Liver (EASL) - European Organisation for Research and Treatment of Cancer (EORTC) guidelines. Eur J Cancer. 2013;49(6):1509-1510.

5

Chong RJ, Abdullah MS, Hossain MM, Telisinghe PU, Chong VH. Rising incidence of primary liver cancer in Brunei Darussalam. Asian Pac J Cancer Prev. 2013;14(6):3473-3477.

6

Golabi P, Fazel S, Otgonsuren M, Sayiner M, Locklear CT, Younossi ZM. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities. Medicine. 2017;96(9):e5904.

7

Haussecker D, Huang Y, Lau A, Parameswaran P, Fire AZ, Kay MA. Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA. 2010;16(4):673-695.

8

Lee YS, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23(22):2639-2649.

9

Yamasaki S, Ivanov P, Hu GF, Anderson P. Angiogenin cleaves tRNA and promotes stress-induced translational repression. J Cell Biol. 2009;185(1):35-42.

10

Balatti V, Nigita G, Veneziano D, et al. tsRNA signatures in cancer. Proc Natl Acad Sci U S A. 2017;114(30):8071-8076.

11

Yang Y, Chen L, Gu J, et al. Recurrently deregulated lncRNAs in hepatocellular carcinoma. Nat Commun. 2017;8:14421.

12

Liu Q, Ding C, Lang X, Guo G, Chen J, Su X. Small noncoding RNA discovery and profiling with sRNAtools based on high-throughput sequencing. Briefings Bioinformat. 2021;22(1):463-473.

13

Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 2011;17(1):10-12.

14

Wei R, Wang J, Su M, et al. Missing value imputation approach for mass spectrometry-based metabolomics data. Sci Rep. 2018;8(1):663.

15

Vlachos IS, Zagganas K, Paraskevopoulou MD, et al. DIANA-miRPath v3. 0: deciphering microRNA function with experimental support. Nucleic Acids Res. 2015;43(W1):W460-W466.

16

Genuer R, Poggi J-M. Tuleau-malot CJPrl. Variable selection using random forests. Pattern Recognit Lett. 2010;31(14):2225-2236.

17

Tibshirani R. Regression shrinkage and selection via the lasso. J Royal Stat Soc. 1996;58(1):267-288.

18

Weng M, Wu D, Yang C, et al. Noncoding RNAs in the development, diagnosis, and prognosis of colorectal cancer. Transl Res. 2017;181:108-120.

19

Zhu L, Li J, Gong Y, et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol Cancer. 2019;18(1):74.

20

Jin F, Guo Z. Emerging role of a novel small non-coding regulatory RNA: tRNA-derived small RNA. ExRNA. 2019;1(1):39.

21

Vychytilova-Faltejskova P, Merhautova J, Machackova T, et al. MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9. Oncogen esis. 2017;6(11):1-14.

22

Liu S, Zhang Y, Huang C, Lin S. miR-215-5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway. J Cell Biochem. 2020;121(2):1475-1490.

23

Zhao H, Chen J, Chen J, et al. miR-192/215-5p act as tumor suppressors and link Crohn's disease and colorectal cancer by targeting common metabolic pathways: An integrated informatics analysis and experimental study. J Cell Physiol. 2019;234(11):21060-21075.

24

Pan WM, Wang H, Zhang XF, et al. miR-210 participates in hepatic ischemia reperfusion injury by forming a negative feedback loop with SMAD4. Hepatology. 2020;72(6):2134-2148.

25

Ji J, Rong Y, Luo CL, et al. Up-regulation of hsa-miR-210 promotes venous metastasis and predicts poor prognosis in hepatocellular carcinoma. Front Oncol. 2018;8:569.

26

Epis MR, Giles KM, Candy PA, Webster RJ, Leedman PJ. miR-331-3p regulates expression of neuropilin-2 in glioblastoma. J Neuro-oncol. 2014;116(1):67-75.

27

Xie RT, Cong XL, Zhong XM, et al. MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma. Oncol Lett. 2018;15(4):4571-4577.

28

Meng W, Tai Y, Zhao H, et al. Downregulation of miR-33a-5p in hepatocellular carcinoma: a possible mechanism for chemotherapy resistance. Med Sci Monit. 2017;23:1295-1304.

29

Tang Y, Zhou J, Hooi SC, Jiang YM, Lu GD. Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases. Oncol Lett. 2018;16(2):1390-1396.

30

Montagner A, Le Cam L, Guillou HJG. β-catenin oncogenic activation rewires fatty acid catabolism to fuel hepatocellular carcinoma. Gut. 2019;68(2):183-185.

Genes & Diseases
Pages 393-400
Cite this article:
Zuo Y, Chen S, Yan L, et al. Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer. Genes & Diseases, 2022, 9(2): 393-400. https://doi.org/10.1016/j.gendis.2021.01.006

359

Views

4

Downloads

15

Crossref

16

Web of Science

16

Scopus

0

CSCD

Altmetrics

Received: 02 November 2020
Revised: 15 December 2020
Accepted: 20 January 2021
Published: 28 January 2021
© 2021, Chongqing Medical University. Production and hosting by Elsevier B.V.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return