Salivary microRNA for diagnosis of systemic diseases and malignant tumors: a systematic review
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1
University of Parma, Department of Medicine and Surgery, Italy
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2
Azienda Ospedaliero-Universitaria di Parma, Department of General and Specialistic Medicine, Italy
Aim. Salivary transcriptomics is an relatively new field of research that will probably allow in the next feature the development of some non-invasive diagnostic techniques. Among transcripts, microRNAs (miRNA) , small non-coding RNA molecules which regulate the expression of target genes seem to be the most promising molecules. Expression of several miRNAs are associated with the development of specific human diseases, including malignant tumours.
The aim of the present research is to perform a systematic review in order to establish if there is scientific evidence supporting the role of salivary miRNA for the diagnosis of systemic diseases and malignant tumors.
Materials and Methods. We searched into the Medline database, using as entry terms “salivary microRNA”, “saliva and microRNA”, “saliva and tumor”, “saliva and cancer”, “saliva and carcinoma”, “saliva and malignancies” and “saliva and systemic diseases”. Only articles in English and published after 2000 were included in the review.
Inclusion criteria were established including only studies specifically reporting data on saliva sample; studies analyzing peculiar microRNA; studies evaluating patients with systemic diseases where miRNA were used diagnostic purpose. We excluded studies on animals or in vitro samples and papers dealing with systemic microbial infections, hormones, drug dosage. Case reports, conference proceedings, personal communication and reviews were also excluded. We further excluded researches investigating salivary biomarkers in patients with systemic diseases with oral, oropharyngeal and esophageal involvement. References listed in reviews, were screened in order to identify papers possibly missing from the database search. From each studies we extrapolated title, authors, publication year, systemic diseases, type of miRNA, devices used for analyse the samples and significances of results. We divided studies on the basis of the disease. Qualitative analysis was performed using as tool for quality score assessment the guidelines provided by the National Institute of Health (NIH - scores ranging from “poor” to “good”).
Results. The preliminary research initially obtained 12327 papers. After exclusion of repetition 3422 papers were included for further evaluation. The evaluation of title, abstract and the application of inclusion and exclusion criteria eventually led to the identification of 6 articles. One more study was obtained from screening of reference list.
Four studies were focused on pancreatic cancer (among others miRNA identified were the following: miR‑1246, miR‑3976, miR‑4306,miR‑4644, miR-21,miR-34a, miR-155, miR-196a, miR-200b, miR-376a, hsa-miR-23a, hsa-miR-23b, miR-29c, hsa-miR-210, miR-4433-5p, miR-4665-3p, miR-940, miR-1273g-3p, miR-3676-5p, miR-3679-5p, miR-3940-5p, miR-4327, miR-4442 and miR-5100), one on bowel inflammatory diseases (miRNA identified: miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375), one on colorectal cancer (miR-21) and one on prostate cancer (miR-141, miR-21). Six articles searched miRNA through quantitative real-time PCR and one article used RNA microarray. Most of studies (6 on seven) obtained statistically significant association between miRNA and the specific disease. Only one study obtained no significant results. Following the NIH guidelines, 5 studies were scored as “fair” (4 studies on pancreatic cancer and one on colorectal cancer) and two studies were scored as “poor” (bowel inflammatory diseases and prostate cancer). No one of the papers could be identified has having a “good” quality.
Discussion. The results of our review highlight the paucity of papers focused on early diagnosis of systemic diseases through salivary miRNA. The few number and the low quality of articles show the necessity of more comprehensive studies. More studies are needed, also on the basis of the encouraging results obtained from each experiment (statistically significant correlation) and the relatively high quantitative of such molecules in saliva. Particularly, mir21 seems to be the salivary miRNA molecule present in most of the diseases studied.
References
1. Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer. J. Du, L. Zhang. Oncol Lett. 2017 Aug;14(2):1387-1394.
2. miR 1246 and miR 4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer. Machida T, Tomofuji T, Maruyama T, Yoneda T, Ekuni D, Azuma T, Miyai H, Mizuno H, Kato H, Tsutsumi k, Uchida D, Takaki A, Okada H, Morita M. Oncol Rep. 2016 Oct;36(4):2375-81.
3. miRNA-21 and miRNA-34a are potential minimally invasive biomarkers for the diagnosis of pancreatic ductal adenocarcinoma. Alemar B, Izetti P, Gregòrio C, Macedo GS, Castro MA, Osvaldt AB, Matte U, Ashton-Prolla P. Pancreas. 2016 Jan;45(1):84-92.
Keywords:
salivary diagnostic,
microRNA,
Systemic diseases,
Malignant tumors,
Systematic review
Conference:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.
Presentation Type:
Poster Presentation
Topic:
Salivary Research
Citation:
Viani
M,
Pezzi
M,
Casali
E,
Musolino
A,
Vescovi
P and
Meleti
M
(2019). Salivary microRNA for diagnosis of systemic diseases and malignant tumors: a systematic review.
Front. Physiol.
Conference Abstract:
5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine..
doi: 10.3389/conf.fphys.2019.27.00063
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Received:
05 Nov 2018;
Published Online:
09 Dec 2019.
*
Correspondence:
Dr. Maria Vittoria Viani, University of Parma, Department of Medicine and Surgery, Parma, Emilia-Romagna, 43121, Italy, mariavittoriaviani@gmail.com