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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 5  |  Page : 6-10  

Fibroblastic growth factor as a diagnostic and prognostic marker in odontogenic cysts and tumors: A systematic review


1 Department of Oral and Maxillofacial Pathology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
2 Peterson Dental Clinic, Tenkasi District, Tamil Nadu, India

Date of Submission23-Sep-2020
Date of Acceptance24-Sep-2020
Date of Web Publication05-Jun-2021

Correspondence Address:
Gururaj Narayana Rao
Department of Oral and Maxillofacial Pathology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpbs.JPBS_563_20

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   Abstract 


Cellular signaling proteins maintain the basic activities of cell and communication, between the cells for normal growth and development and pathological situation as well. Fibroblast growth factor (FGF) and fibroblast growth factor receptors (FGFRs) have a comparatively huge part to play in the cellular communication processes. Human FGF has 22 members, 18 ligands, and 4 tyrosine kinase receptors for binding and is expressed in a wide range of cells. Any alteration in these factors would disrupt their normal function, leading to various abnormalities. The aim of this systematic analysis, is to understand the FGFs, the physiological and pathological role of FGF in oral diseases, and to predict the use of FGF in the predilection toward odontogenic cyst and tumors. This review helps confer the role of FGF in various physiological and pathological aspects in systemic diseases and analyzes its role in diagnosis and prognosis of odontogenic cysts and tumors.

Keywords: Fibroblast growth factor, mutations, odontogenic tumors and cyst, receptor signaling


How to cite this article:
Rao GN, Rosaian AS, Jawahar G, Raj P H, Rachel J B, Emmanuel P B. Fibroblastic growth factor as a diagnostic and prognostic marker in odontogenic cysts and tumors: A systematic review. J Pharm Bioall Sci 2021;13, Suppl S1:6-10

How to cite this URL:
Rao GN, Rosaian AS, Jawahar G, Raj P H, Rachel J B, Emmanuel P B. Fibroblastic growth factor as a diagnostic and prognostic marker in odontogenic cysts and tumors: A systematic review. J Pharm Bioall Sci [serial online] 2021 [cited 2021 Oct 26];13, Suppl S1:6-10. Available from: https://www.jpbsonline.org/text.asp?2021/13/5/6/317533




   Introduction Top


Fibroblast growth factors (FGFs) are proteinaceous substances that act in many biological, physiological, functional, and developmental processes.[1] FGF ligands in combination with fibroblast growth factor receptors (FGFRs, respective receptors) exhibit various controlled signaling pathways that bring about specific and regulated cellular responses. Any type of modification or mutation that causes changes in the FGF/FGFR signaling results in various types of abnormalities.[1] Point mutations, genetic alterations, and other related chromosomal aberrations that result in splice variants and altered FGFs have the potential to form cancer.[2] In the investigative protocols using the generation sequencing technique, conclusive results showed that a small amount (7% of cancers) is characterized by FGF–FGFR gene alterations. These include around 66% of lesions, which are caused because of FGFR–FGF gene amplification, 26% due to gene mutations, and 8% caused because of gene rearrangements. Although the role of FGF in the odontogenic cysts and tumors was studied by various authors, they are yet to establish its genetic predisposition.[3] Therefore, we have planned to do a cumulative study that would focus on the genetic predisposition. The review analyzes the role of FGF in various odontogenic lesions studies so far and the possibility of using it as a predictive, diagnostic, and prognostic marker.

Aim

The aim of this study is to understand the FGFs and its physiological and pathological role of FGF in oral diseases, based on the analysis of the collected articles, and to predict the use of FGF in the predilection toward odontogenic cyst and tumors


   Materials and Methods Top


This systematic review was analyzed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement Criteria (Moher, Liberati, Tetzlaff, Altman, and PRISMA Group, 2010) [Figure 1].
Figure 1: PRISMA flowchart of the systematic review

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Inclusion criteria

In this review, we included full papers available in the English literature that were published after 1980; all peer-reviewed articles; observational studies such as cohort, case–control, and retrospective studies; all the articles that used to know the physiological and pathological role in oral diseases; and clinical and research-oriented application in oral lesions. Thus, we included those articles that used to predict the use of FGF in determining genetic predisposition.

Exclusion criteria

All the duplicates and abstract-only articles were excluded. Articles that used markers only to diagnose epithelial neoplasm were also excluded.

Sources, search strategy, and study selection

Cochrane Database of Systematic Reviews, Embase, Medline, Sci-Expanded, PubMed, and PubMed Central were searched to identify the records relating to this review.


   Results Top


The systematic analysis shows the role of fibroblastic growth factor in physiological and pathological processes (as Tabulated in [Table 1], [Table 2], [Table 3], [Table 4])
Table 1: Systematic review search strategy for PubMed, Embase, and Cochrane

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Table 2: Author details, fibroblastic growth factor, genetic mutation, and the role caused in disease

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Table 3: Fibroblastic growth factor and their physiological role

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Table 4: Fibroblastic growth factor and their clinical uses

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.


   Discussion Top


FGF has a very important role to play in every aspects of embryogenesis, and its manifestation is highly appreciable in the growth and development of an individual. FGF and the FGFR ligands along with their signaling network play an important role in the process of odontogenesis.[4],[5]

At the initiation stage, once enamel formation begins following the signals from odontogenic epithelium, FGF 8, FGF 9, and FGF 17 are expressed.[6],[7],[8],[9],[10] Similarly, FGF 10 is expressed in the mesenchyme, during the initial phases of the formation of dentin and surrounding bony arrangement.[5],[11], [12,[13],[14],[15] The overall physiological role of each FGF is tabulated in Table 3.

A comprehensive collection of studies showing mutation of the FGF gene and the pathologies involved is analyzed in Table 2 and its clinical applications is summarized in Table 4.

From the review, we could identify that FGF 1, FGF 2, and FGF 8 are studied in the odontogenic tumors and cyst.

However, the role of FGF in odontogenic cyst and tumors as effective as a diagnostic, prognostic, and predictive biomarker is yet to be studied. Further, it is much more evocative to identify its role as a predictive marker in the odontogenic tumors and odontogenic cysts.

Limitations and future perspective

The protagonist action of FGF as a biomarker for the genetic predisposition of odontogenic tumors and odontogenic cysts is still inconclusive. Thus, studies conducting on a large scale using FGF in the dental follicle and odontogenic epithelium surrounding the impacted tooth may be beneficial in predicting the pathological changes.


   Conclusion Top


This systematic review gives an insight into the physiological role of Fibroblastic Growth Factor, and the pathologies that are associated with the various gene alterations. Such analysis helps in diagnosis and determining the prognosis of various Odontogenic cysts and tumors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Khalid A, Javaid MA. Fibroblast growth factors and their emerging cancer related aspects. J Cancer Sci Ther 2016;8:190 -205.  Back to cited text no. 1
    
2.
Ghedini GC, Ronca R, Presta M, Giacomini A. Future applications of FGF/FGFR inhibitors in cancer. Exp Rev Anticancer Ther 2018;18:861-72.  Back to cited text no. 2
    
3.
Du W, Du W, Yu H. The role of fibroblast growth factors in tooth development and incisor renewal. Stem Cells Int 2018;2018:7549160.  Back to cited text no. 3
    
4.
Ornitz1 DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol 2015;4:215-66.  Back to cited text no. 4
    
5.
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010;141:1117-34.  Back to cited text no. 5
    
6.
Porntaveetus T, Otsuka Tanaka Y, Basson MA, Moon AM, Sharpe PT, Ohazama A. Expression of fibroblast growth factors (FGFs) in murine tooth development. J Anat 2011;218:534-43.  Back to cited text no. 6
    
7.
So F, Daley TD, Jackson L, Wysocki GP. Immunohistochemical localization of fibroblast growth factors FGF 1 and FGF 2, and receptors FGFR2 and FGFR3 in the epithelium of human odontogenic cysts and tumors. J Oral Pathol Med 2001;30:428-33.  Back to cited text no. 7
    
8.
Garg K, Chandra S, Raj V, Fareed W, Zafar M. Molecular and genetic aspects of odontogenic tumors: A review. Iran J Basic Med Sci 2015;18:529-36.  Back to cited text no. 8
    
9.
Nakao Y, Mitsuyasu T, Kawano S, Nakamura N, Kanda S, Nakamura S. Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen activated protein kinase pathway. Int J Oncol 2013;43:1377-84.  Back to cited text no. 9
    
10.
Jiang C, Xu Q, Zhang Q, Wang S, Carrasco LR, Le AD. Benign odontogenic tumors: Origins, immunophenotypic features, and genetic alterations. Curr Oral Health Rep 2016;3:93-101.  Back to cited text no. 10
    
11.
Liu A, Wu M, Guo X, Guo H, Zhou Z, Wei K, et al. Clinical, pathological, and genetic evaluations of Chinese patient with otodental syndrome and multiple complex odontoma: Case report. Medicine 2017;96:e6014.  Back to cited text no. 11
    
12.
Swarup N, Nayak MT, Chowdhary Z, Mehendiratta M, Khatana S, Choi SJ, et al. Evaluation and immunolocalization of BMP4 and FGF8 in odontogenic cyst and tumors. Anal Cell Pathol 2018;2018:1204549.  Back to cited text no. 12
    
13.
Küchler EC, Lips A, Tannure PN, Ho B, Costa MC, Granjeiro JM, et al. Tooth agenesis association with self reported family history of cancer. J Dent Res 2013;92:149-55.  Back to cited text no. 13
    
14.
Lee SK, Kim YS. Current concepts and occurrence of epithelial odontogenic tumors: I. Ameloblastoma and adenomatoid odontogenic tumor. Korean J Pathol 2013;47:191-202.  Back to cited text no. 14
    
15.
Küchler EC, Sabóia TM, Vieira TC, Lips A, Tannure PN, Deeley K, et al. Studies of genes involved in craniofacial development and tumorigenesis: FGF3 contributes to isolated oral clefts and may interact with PAX9. Acta Odontol Scand 2014;72:1070-8.  Back to cited text no. 15
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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