Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers

Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers Houman Kahroba Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0003-1544-4547 Nasser Samadi Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Mostafa Mostafazadeh Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Mohamad Saied Hejazi Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0002-1033-3998 Mohammad Reza Sadeghi Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran Shahryar Hashemzadeh Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Amir Taher Eftekhar Sadat Department of General and Vascular Surgery, Imam Reza Educational Hospital, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Abbas Karimi Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential. Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals. Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome. Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.
11 06 2021 11 06 2021 127 138 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2020-06-06 2021-02-27 2021-11-06 10.34172/bi.2021.22178 20220328130841 https://bi.tbzmed.ac.ir/Article/bi-22178 https://bi.tbzmed.ac.ir/PDF/bi-12-127.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-127.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-127.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-127.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-127.pdf 10.1007/s00018-019-03035-2 10.1097/01.sla.0000149300.28588.23 10.5152/ucd.2015.2811 10.1186/s12885-017-3738-y 10.1007/s10120-019-00995-z 10.3346/jkms.2018.33.e190 10.1002/ijc.26430 10.3892/or.2014.3014 10.1016/j.apsb.2016.09.002 10.1158/1078-0432.ccr-13-3173 10.1080/14728222.2017.1389900 10.1016/s0092-8674(04)00045-5 10.1038/nature03702 10.1016/s1470-2045(09)70343-2 10.1073/pnas.0804549105 10.1016/j.molonc.2014.02.009 10.1016/j.canlet.2010.07.018 10.1002/jcp.28374 10.1016/j.bbrc.2017.10.003 10.3233/cbm-170738 10.1371/journal.pone.0170628 10.1021/acsnano.9b01004 10.1093/bioinformatics/bty852 10.1007/978-1-4939-2547-6_10 10.1021/acs.langmuir.7b04080 10.1007/s00216-014-8040-0 10.1002/9781118468869.ch3 Wang W, Young MR, Srivastava S. MicroRNA Biomarkers for Early Detection of Cancer. In: Srivastava S, ed. Biomarkers in Cancer Screening and Early Detection. 2017. p. 27-36. 10.1002/9781118468869.ch5 Lee J, Ghosh S, Srivastava S. Exosomes: A Valuable Biomedical Tool in Biomarker Discovery and Development. In: Srivastava S, ed. Biomarkers in Cancer Screening and Early Detection. 2017. p. 50-63. 10.7150/jca.27457 10.1177/1010428317695012 10.3892/ol.2016.5544 10.3892/ol.2014.2232 10.1186/s12943-019-1001-7 10.1155/2017/1526981 10.18632/oncotarget.6736 10.1111/jgh.13041 10.1007/s10120-014-0363-1 10.1155/2018/8545347 10.3390/ijms20194684 10.1080/20013078.2018.1555410 10.1016/j.ymeth.2012.01.002 10.1016/j.ajpath.2013.09.027