Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Biomarkers | Research article

Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma

Authors: Lirong Wu, Kexiao Zheng, Cheng Yan, Xuan Pan, Yatian Liu, Juying Liu, Feijiang Wang, Wenjie Guo, Xia He, Jiong Li, Ye Shen

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection.

Methods

Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.

Results

Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%).

Conclusions

This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tang LL, Chen WQ, Xue WQ, He YQ, Zheng RS, Zeng YX, Jia WH. Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett. 2016;374(1):22–30.CrossRefPubMed Tang LL, Chen WQ, Xue WQ, He YQ, Zheng RS, Zeng YX, Jia WH. Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer Lett. 2016;374(1):22–30.CrossRefPubMed
2.
3.
go back to reference Chan K, Jks W, King A, Bcy Z, Wkj L, Chan SL, Chu S, Mak C, Iol T, Sym L. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377(6):513.CrossRef Chan K, Jks W, King A, Bcy Z, Wkj L, Chan SL, Chu S, Mak C, Iol T, Sym L. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377(6):513.CrossRef
4.
go back to reference Ho SL, Chan HM, Ha AW, Wong RN, Li HW. Direct quantification of circulating miRNAs in different stages of nasopharyngeal cancerous serum samples in single molecule level with total internal reflection fluorescence microscopy. Anal Chem. 2014;86(19):9880.CrossRefPubMed Ho SL, Chan HM, Ha AW, Wong RN, Li HW. Direct quantification of circulating miRNAs in different stages of nasopharyngeal cancerous serum samples in single molecule level with total internal reflection fluorescence microscopy. Anal Chem. 2014;86(19):9880.CrossRefPubMed
5.
go back to reference Gong D, Li Z, Ding R, Cheng M, Huang H, Liu A, Kang M, He H, Xu Y, Shao J. Extensive serum biomarker analysis in patients with nasopharyngeal carcinoma. Cytokine. 2019;118:107–14.CrossRefPubMed Gong D, Li Z, Ding R, Cheng M, Huang H, Liu A, Kang M, He H, Xu Y, Shao J. Extensive serum biomarker analysis in patients with nasopharyngeal carcinoma. Cytokine. 2019;118:107–14.CrossRefPubMed
6.
go back to reference Wang Y, Zhao Q, Lan N, Wang S. Identification of methylated genes and miRNA signatures in nasopharyngeal carcinoma by bioinformatics analysis. Mol Med Rep. 2018;17(4):4909.PubMedPubMedCentral Wang Y, Zhao Q, Lan N, Wang S. Identification of methylated genes and miRNA signatures in nasopharyngeal carcinoma by bioinformatics analysis. Mol Med Rep. 2018;17(4):4909.PubMedPubMedCentral
7.
8.
go back to reference Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57(5):675–87.CrossRefPubMed Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57(5):675–87.CrossRefPubMed
9.
go back to reference Danish S, Maha A. MicroRNAs in development and disease. Physiol Rev. 2011;91(3):827–87.CrossRef Danish S, Maha A. MicroRNAs in development and disease. Physiol Rev. 2011;91(3):827–87.CrossRef
10.
go back to reference Srikumar S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Yu-Juen C, Chien-Jen C, Allan H, Bill S, Paul A. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A. 2008;105(15):5874–8.CrossRef Srikumar S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Yu-Juen C, Chien-Jen C, Allan H, Bill S, Paul A. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A. 2008;105(15):5874–8.CrossRef
11.
go back to reference Yu B-L, Peng X-H, Zhao F-P, Liu X, Lu J, Wang L, Li G, Chen H-H, Li X-P. MicroRNA-378 functions as an onco- miR in nasopharyngeal carcinoma by repressing TOB2 expression. Int J Oncol. 2014;44(4):1215–22.CrossRefPubMed Yu B-L, Peng X-H, Zhao F-P, Liu X, Lu J, Wang L, Li G, Chen H-H, Li X-P. MicroRNA-378 functions as an onco- miR in nasopharyngeal carcinoma by repressing TOB2 expression. Int J Oncol. 2014;44(4):1215–22.CrossRefPubMed
12.
go back to reference Jeff B. Fei-Fei. MicroRNAs in nasopharyngeal carcinoma. Chin J Cancer. 2014;33(11):539–44.CrossRef Jeff B. Fei-Fei. MicroRNAs in nasopharyngeal carcinoma. Chin J Cancer. 2014;33(11):539–44.CrossRef
13.
go back to reference Croce C. Introduction to the role of microRNAs in cancer diagnosis, prognosis, and treatment. Cancer J. 2012;18(3):213.CrossRefPubMed Croce C. Introduction to the role of microRNAs in cancer diagnosis, prognosis, and treatment. Cancer J. 2012;18(3):213.CrossRefPubMed
14.
go back to reference Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosovaagadjanyan EL, Stirewalt DL. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108(12):5003–8.CrossRefPubMedPubMedCentral Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosovaagadjanyan EL, Stirewalt DL. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108(12):5003–8.CrossRefPubMedPubMedCentral
15.
go back to reference Xie Z, Chen G, Zhang X, Li D, Huang J, Yang C, Zhang P, Qin Y, Duan Y, Gong B. Salivary microRNAs as promising biomarkers for detection of esophageal cancer. PLoS One. 2013;8(4):e57502.CrossRefPubMedPubMedCentral Xie Z, Chen G, Zhang X, Li D, Huang J, Yang C, Zhang P, Qin Y, Duan Y, Gong B. Salivary microRNAs as promising biomarkers for detection of esophageal cancer. PLoS One. 2013;8(4):e57502.CrossRefPubMedPubMedCentral
16.
go back to reference Du J, Zhang L. Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer. Oncol Lett. 2017;14(2):1387–94.CrossRefPubMedPubMedCentral Du J, Zhang L. Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer. Oncol Lett. 2017;14(2):1387–94.CrossRefPubMedPubMedCentral
17.
go back to reference Pan JJ, Ng WT, Zong JF, Chan LL, O'Sullivan B, Lin SJ, et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer. 2016;122:546–58.CrossRefPubMed Pan JJ, Ng WT, Zong JF, Chan LL, O'Sullivan B, Lin SJ, et al. Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy. Cancer. 2016;122:546–58.CrossRefPubMed
18.
go back to reference Gallo A, Alevizos I. Isolation of circulating microRNA in saliva. Methods Mol Biol. 2013;1024(1024):183–90.CrossRefPubMed Gallo A, Alevizos I. Isolation of circulating microRNA in saliva. Methods Mol Biol. 2013;1024(1024):183–90.CrossRefPubMed
19.
go back to reference Duan D, Zheng KX, Shen Y, Cao R, Jiang L, Lu Z, Yan X, Li J. Label-free high-throughput microRNA expression profiling from total RNA. Nucleic Acids Res. 2011;39(22):e154.CrossRefPubMedPubMedCentral Duan D, Zheng KX, Shen Y, Cao R, Jiang L, Lu Z, Yan X, Li J. Label-free high-throughput microRNA expression profiling from total RNA. Nucleic Acids Res. 2011;39(22):e154.CrossRefPubMedPubMedCentral
20.
go back to reference Bartel D, MicroRNAs P. Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRef Bartel D, MicroRNAs P. Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRef
21.
go back to reference Liu N, Cui RX, Sun Y, Guo R, Mao YP, Tang LL, Jiang W, Liu X, Cheng YK, He QM. A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma. Int J Cancer. 2014;134(6):1359–68.CrossRefPubMed Liu N, Cui RX, Sun Y, Guo R, Mao YP, Tang LL, Jiang W, Liu X, Cheng YK, He QM. A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma. Int J Cancer. 2014;134(6):1359–68.CrossRefPubMed
22.
go back to reference Zeng X, Xiang J, Wu M, Xiong W, Tang H, Deng M, Li X, Liao Q, Su B, Luo Z. Circulating miR-17, miR-20a, miR-29c, and miR-223 combined as non-invasive biomarkers in nasopharyngeal carcinoma. PLoS One. 2012;7(10):e46367.CrossRefPubMedPubMedCentral Zeng X, Xiang J, Wu M, Xiong W, Tang H, Deng M, Li X, Liao Q, Su B, Luo Z. Circulating miR-17, miR-20a, miR-29c, and miR-223 combined as non-invasive biomarkers in nasopharyngeal carcinoma. PLoS One. 2012;7(10):e46367.CrossRefPubMedPubMedCentral
23.
go back to reference Erbes T, Hirschfeld M, Rücker G, Jaeger M, Boas J, Iborra S, Mayer S, Gitsch G, Stickeler E. Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker. BMC Cancer. 2015;15(1):193.CrossRefPubMedPubMedCentral Erbes T, Hirschfeld M, Rücker G, Jaeger M, Boas J, Iborra S, Mayer S, Gitsch G, Stickeler E. Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker. BMC Cancer. 2015;15(1):193.CrossRefPubMedPubMedCentral
24.
go back to reference Heidi S, Andreia Machado DS, George C, Klaus P. Data normalization strategies for MicroRNA quantification. Clin Chem. 2015;61(11):1333–42.CrossRef Heidi S, Andreia Machado DS, George C, Klaus P. Data normalization strategies for MicroRNA quantification. Clin Chem. 2015;61(11):1333–42.CrossRef
25.
go back to reference Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, Wang JF, Zhang Z, Lu S, Huang X. Plasma MicroRNA panel to diagnose hepatitis B virus–related hepatocellular carcinoma. J Clin Oncol. 2011;29(36):4781.CrossRefPubMed Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z, Wang JF, Zhang Z, Lu S, Huang X. Plasma MicroRNA panel to diagnose hepatitis B virus–related hepatocellular carcinoma. J Clin Oncol. 2011;29(36):4781.CrossRefPubMed
26.
go back to reference Murray MJ, Bell E, Raby KL, Rijlaarsdam MA, Gillis AJ, Looijenga LH, Brown H, Destenaves B, Nicholson JC, Coleman N. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. Br J Cancer. 2016;114(2):151–62.CrossRefPubMed Murray MJ, Bell E, Raby KL, Rijlaarsdam MA, Gillis AJ, Looijenga LH, Brown H, Destenaves B, Nicholson JC, Coleman N. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. Br J Cancer. 2016;114(2):151–62.CrossRefPubMed
27.
go back to reference Agaoglu FY, Dizdar Y, Dogan O, Alatli C, Ayan I, Savci N, Tas S, Dalay N, Altun M. P53 overexpression in nasopharyngeal carcinoma. Vivo. 2004;18(5):555–60. Agaoglu FY, Dizdar Y, Dogan O, Alatli C, Ayan I, Savci N, Tas S, Dalay N, Altun M. P53 overexpression in nasopharyngeal carcinoma. Vivo. 2004;18(5):555–60.
29.
go back to reference Wang HB, Zhang H, Zhang JP, Li Y, Zhao B, Feng GK, Du Y, Xiong D, Zhong Q, Liu WL. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Nat Commun. 2015;6:6240.CrossRefPubMedPubMedCentral Wang HB, Zhang H, Zhang JP, Li Y, Zhao B, Feng GK, Du Y, Xiong D, Zhong Q, Liu WL. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Nat Commun. 2015;6:6240.CrossRefPubMedPubMedCentral
Metadata
Title
Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma
Authors
Lirong Wu
Kexiao Zheng
Cheng Yan
Xuan Pan
Yatian Liu
Juying Liu
Feijiang Wang
Wenjie Guo
Xia He
Jiong Li
Ye Shen
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Biomarkers
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-6037-y

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine