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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2022; 28(6): 653-664
Published online Feb 14, 2022. doi: 10.3748/wjg.v28.i6.653
Atrophic gastritis and gastric cancer tissue miRNome analysis reveals hsa-miR-129-1 and hsa-miR-196a as potential early diagnostic biomarkers
Greta Varkalaite, Evelina Vaitkeviciute, Ruta Inciuraite, Violeta Salteniene, Simonas Juzenas, Vytenis Petkevicius, Rita Gudaityte, Antanas Mickevicius, Alexander Link, Limas Kupcinskas, Marcis Leja, Juozas Kupcinskas, Jurgita Skieceviciene
Greta Varkalaite, Evelina Vaitkeviciute, Ruta Inciuraite, Violeta Salteniene, Simonas Juzenas, Limas Kupcinskas, Jurgita Skieceviciene, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Vytenis Petkevicius, Juozas Kupcinskas, Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Rita Gudaityte, Antanas Mickevicius, Department of Surgery, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
Alexander Link, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
Marcis Leja, Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga 1586, Latvia
Author contributions: Varkalaite G, Leja M, Kupcinskas L, Kupcinskas J and Skieceviciene J contributed to study conception and designed the research; Gudaityte R, Petkevicius V and Mickevicius A collected material and clinical data from the participants; Varkalaite G and Vaitkeviciute E performed all the investigations, analysis of data and drafted the manuscript; Juzenas S and Inciuraite R reviewed and edited the manuscript; Salteniene V revised the article for important intellectual content; Link A, Kupcinskas J and Skieceviciene J approved the final version of the manuscript.
Supported by the MULTIOMICS project that has received funding from European Social Fund (No. 09.3.3-LMT-K-712-01-0130) under grant agreement with the Research Council of Lithuania (LMTLT).
Institutional review board statement: The study was approved by the Kaunas Regional Biomedical Research Ethics Committee.
Informed consent statement: All study participants provided informed consent prior to study enrollment.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jurgita.skieceviciene@lsmuni.lt.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jurgita Skieceviciene, PhD, Senior Researcher, Institute for Digestive Research, Lithuanian University of Health Sciences, A. Mickeviciaus street 9, Kaunas 44307, Lithuania. jurgita.skieceviciene@lsmuni.lt
Received: September 13, 2021
Peer-review started: September 13, 2021
First decision: November 16, 2021
Revised: November 19, 2021
Accepted: January 19, 2022
Article in press: January 19, 2022
Published online: February 14, 2022
Processing time: 148 Days and 14.2 Hours
ARTICLE HIGHLIGHTS
Research background
Gastric cancer (GC) is a complex disease arising from the interaction of environmental (e.g., diet, smoking, etc.) and host-associated factors [e.g., Helicobacter pylori (H. pylori) infection, genetics, etc.]. Due to its silent course, it is also one of the most lethal cancers worldwide as it is usually diagnosed at the advanced stages.
Research motivation
Novel biomarkers that would help to improve GC patients’ diagnosis and prognosis are highly needed. Studies show that microRNAs (miRNAs) play an important role in many cancers and could be a promising biomarker or even therapeutic target.
Research objectives
The objectives of the study were to analyze whole miRNome profiles of control, premalignant and malignant gastric tissues, and select the potential miRNA markers that could have a potential for minimally invasive GC diagnostics.
Research methods
Total RNA from gastric tissue samples was subjected for small RNA sequencing (smRNA-seq). Plasma total circulating nucleic acids were used for the expression analysis of the most tissue deregulated miRNAs by real-time quantitative polymerase chain reaction. Statistical analysis involved the differential expression and discrimination analyses.
Research results
The abundance of altered expression miRNAs corresponded to a pathological cascade of GC development. Hsa-miR-129-1-3p and has-miR-196a-5p were shown to be deregulated in healthy-premalignant-malignant sequence. In addition to this, we showed that down-regulation of hsa-miR-129-1-3p could also be detected non-invasively in GC patients’ plasma samples. Finally, results indicated that hsa-miR-215-3p/5p and hsa-miR-934 were significantly deregulated based on H. pylori infection status for GC patients.
Research conclusions
Gastric tissue miRNome study provides extensive profiling of control, premalignant and malignant cases. Based on smRNA-seq results several miRNAs were shown as potential gastric carcinogenesis (hsa-miR-196a-5p and hsa-miR-129-1-3p); and H. Pylori-related (hsa-miR-215-3p/5p and hsa-miR-934) biomarkers.
Research perspectives
This study provides novel insights into complex GC pathogenesis cascade and could serve as a reference for future research to support our findings.
