Abstract
MicroRNA-21 (miR-21) expression was quantified by real-time qRT-PCR in peripheral blood and saliva samples obtained from patients diagnosed with colorectal cancer (CRC) of varying degrees of malignancy and healthy volunteers. All patients had adenocarcinoma located in the distal colon at different stages. Significant differences were detected between the control group and the total experimental group of CRC patients (plasma, P = 0.0001; saliva, P = 5e-12). MiR-21 expression was also significantly different in certain subgroups of patients with CRC disease stages II–IV as compared to the control group. No correlation of miR-21 expression was found with regard to gender and age of patents. Also, there were no significant individual correlations and linear regression of miR-21 expression in the plasma and saliva. The estimated diagnostic sensitivity and specificity of miR-21 expression were respectively 65 and 85% in the plasma, and 97 and 91% in the saliva. Our data suggest that miR-21 in both the saliva and plasma could be a proper biomarker for CRC screening, although the saliva miR-21 expression test looks preferable due to its higher sensitivity, specificity, and technical simplicity.
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References
Aslam MI, Taylor K, Pringle JH, Jameson JS (2009) MicroRNAs are novel biomarkers of colorectal cancer. Br J Surg 96(7):702–710. doi:10.1002/bjs.6628
Beckett EL, Martin C, Choi JH, King K, Niblett S, Boyd L, Duesing K, Yates Z, Veysey M, Lucock M (2015) Folate status, folate-related genes and serum miR-21 expression: implications for miR-21 as a biomarker. BBA Clin 4:45–51. doi:10.1016/j.bbacli.2015.06.006
Chen XJ, Shi KQ, Wang YQ, Song M, Zhou W, Tu HX, Lin Z (2015) Clinical value of integrated-signature miRNAs in colorectal cancer: miRNA expression profiling analysis and experimental validation. Oncotarget 6(35):37544–37556. doi:10.18632/oncotarget.6065
Dhayat SA, Mardin WA, Seggewiß J, Ströse AJ, Matuszcak C, Hummel R, Senninger N, Mees ST, Haier J (2015) MicroRNA profiling implies new markers of gemcitabine chemoresistance in mutant p53 pancreatic ductal adenocarcinoma. PLoS One 10(11):e0143755. doi:10.1371/journal.pone.0143755
Faber C, Kirchner T, Hlubek F (2009) The impact of microRNAs on colorectal cancer. Virchows Arch 454:359–367
Florkowski CM (2008) Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests. Clin Biochem Rev 29(Suppl 1):S83–S87
Fukusima Y, Linuma H, Tsukamoto M, Matsuda K, Hashiguchi Y (2015) Clinical significance of microRNA-21 as biomarker in each Dukes’ stage of colorectal cancer. Oncol Rep 33(2):573–582. doi:10.3892/or.2014.3614
Hermansen SK, Nielsen BS, Aaberg-Jessen C, Kristensen BW (2015) miR-21 is linked to glioma angiogenesis: a co-localization study. J Histochem Cytochem. doi:10.1369/0022155415623515
Iorio MV, Croce CM (2012) microRNA involvement in human cancer. Carcinogenesis 33(6):1126–1133. doi:10.1093/carcin/bgs140
Kwekel JC, Vijay V, Desai VG, Moland CL, Fuscoe JC (2015) Age and sex differences in kidney microRNA expression during the life span of F344 rats. Biol Sex Differ 6(1):1. doi:10.1186/s13293-014-0019-1,
Liu CJ, Lin SC, Yang CC, Cheng HW, Chang KW (2012) Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck 34(2):219–224. doi:10.1002/hed.21713
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-∆∆Ct method. Methods 25:402–408
Mazeh H, Mizrahi I, Ilyayev N, Halle D, Brücher B, Bilchik A, Protic M, Daumer M, Stojadinovic A, Itzhak A, Nissan A (2013) The diagnostic and prognostic role of microRNA in colorectal cancer—a comprehensive review. J Cancer 4(3):281–295. doi:10.7150/jca.5836
Noren Hooten N, Fitzpatrick M, Wood WH, De S, Ejiogu N, Zhang Y, Mattison JA, Becker KG, Zonderman AB, Evans MK (2013) Age-related changes in microRNA levels in serum. Aging (Albany NY) 5(10):725–740
Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299(4):425–436. doi:10.1001/jama.299.4.425
Schetter AJ, Nguyen GH, Bowman ED, Mathé EA, Yuen ST, Hawkes JE, Croce CM, Leung SY, Harris CC (2009) Association of inflammation-related and microRNA gene expression with cancer-specific mortality of colon adenocarcinoma. Clin Cancer Res 15(18):5878–5887. doi:10.1158/1078-0432.CCR-09-0627
Sun G, Cheng YW, Lai L, Huang TC, Wang J, Wu X, Wang Y, Huang Y, Wang J, Zhang K, Hu S, Yang JR, Yen Y (2015) Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol. Oncotarget. doi:10.18632/oncotarget.6460
Tang JT, Fang JY (2009) MicroRNA regulatory network in human colorectal cancer. Mini Rev Med Chem 9:921–926
Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A (2013) Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst 105(12):849–859. doi:10.1093/jnci/djt101
Tuck MK, Chan DW, Chia D, Godwin AK, Grizzle WE, Krueger KE, Rom W, Sanda M, Sorbara L, Stass S, Wang W, Brenner DE (2009) Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res 8(1):113–117. doi:10.1021/pr800545q
Wang Y, Gao X, Wei F, Zhang X, Yu J, Zhao H, Sun Q, Yan F, Yan C, Li H, Ren X (2014) Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene 533(1):389–397. doi:10.1016/j.gene.2013.09.038
Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56(11):1733–1741. doi:10.1373/clinchem.2010.147405
Wu X, Li S, Xu X, Wu S, Chen R, Jiang Q, Li Y, Xu Y (2015) The potential value of miR-1 and miR-374b as biomarkers for colorectal cancer. Int J Clin Exp Pathol 8(3):2840–2851
Xia X, Yang B, Zhai X, Liu X, Shen K, Wu Z, Cai J (2013) Prognostic role of microRNA-21 in colorectal cancer: a meta-analysis. PLoS One 8(11):e80426. doi:10.1371/journal.pone.0080426
Xie Z, Chen G, Zhang X, Li D, Huang J, Yang C, Zhang P, Qin Y, Duan Y, Gong B, Li Z (2013) Salivary microRNAs as promising biomarkers for detection of esophageal cancer. PLoS One 8(4):e57502. doi:10.1371/journal.pone.0057502
Xu LF, Wu ZP, Chen Y, Zhu QS, Hamidi S, Navab R (2014) MicroRNA-21 (miR-21) regulates cellular proliferation, invasion, migration, and apoptosis by targeting PTEN, RECK and Bcl-2 in lung squamous carcinoma, Gejiu City, China. PLoS One 9(8):e103698. doi:10.1371/journal.pone.0103698
Ye M, Ye P, Zhang W, Rao J, Xie Z (2014) Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer. Nan Fang Yi Ke Da Xue Xue Bao 34(6):885–889
Zhang C, Liu K, Li T, Fang J, Ding Y, Sun L, Tu T, Jiang X, Du S, Hu J, Zhu W, Chen H, Sun X (2016) miR-21: a gene of dual regulation in breast cancer. Int J Oncol 48(1):161–172. doi:10.3892/ijo.2015.3232
Zhao J, Zhang Y, Zhao G (2015) Emerging role of microRNA-21 in colorectal cancer. Cancer Biomark 15(3):219–226. doi:10.3233/CBM-150468
Zhou X, Wang X, Huang Z, Wang J, Zhu W, Shu Y, Liu P (2014) Prognostic value of miR-21 in various cancers: an updating meta-analysis. PLoS One 9(7):e102413. doi:10.1371/journal.pone.0102413
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Communicated by: Michal Witt
An erratum to this article is available at http://dx.doi.org/10.1007/s13353-016-0386-x.
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Sazanov, A.A., Kiselyova, E.V., Zakharenko, A.A. et al. Plasma and saliva miR-21 expression in colorectal cancer patients. J Appl Genetics 58, 231–237 (2017). https://doi.org/10.1007/s13353-016-0379-9
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DOI: https://doi.org/10.1007/s13353-016-0379-9