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Lichen Planus

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Genomics, Personalized Medicine and Oral Disease

Abstract

Oral Lichen Planus (OLP), a common chronic inflammatory T-cell mediated oral mucocutaneous disease, is a complex oral disease and the management of a complex disorder requires a personalized treatment based on a network approach. Genes involved in different biological processes form complex interaction networks. However, only few of them have a high number of interactions with the other genes in the network and, therefore, they may play a major role.

In previous bioinformatics and experimental studies, these genes were identified and termed as “leader genes”. In the current ab initio theoretical study, genes involved in human OLP pathogenesis are identified and ranked according to their number of interactions, in order to obtain a broader view of its molecular mechanisms and to plan targeted experimentations. Genes involved or potentially involved in OLP were identified by systematically querying several databases until the identification of a final set of genes. Interactions among these genes were mapped and given a significance score using STRING database. For each gene, significance scores were summed to obtain a weighted number of links (WNL) and subsequently genes were clustered according to this parameter. The genes in the highest cluster were termed as leader genes; the other ones were ranked as class B genes, class C genes, and so on. This study was complemented by a topological analysis of the network, carried out using Cytoscape, BinGO and FANMOD software.

Subsequently, in the second part of our study, Class A and Class B genes were used to predict putatively associated microRNAs (miRNAs), exploiting the miRGene database. miRNAs are a family of small and short (usually 19–25 nucleotides long), single-stranded, endogenous, non-coding RNA molecules. They play a key role both in physiology and in pathology, and their role in pathogenesis of oral diseases is emerging. However, despite the importance of incorporating the oral microRNAome in the study of oral disorders, so far only few miRNAs related to them have been discovered and described in the literature. For this reason, we predicited OLP-related miRNAs. Topological properties of the obtained OLP-related microRNAome were also studied.

The interactions in the obtained network showed power law behavior, in agreement with the scale-free topology theory of the biological graphs. One hundred and thirty two genes were identified and five of them (namely, JUN, EGFR, FOS, IL2, ITGB4) were classified as leaders. Interestingly, all of them but EGFR were up-regulated and were widely distributed in the network (in term of topological parameters such as stress, eccentricity and radiality) and showed higher topological coefficients than the other genes.

Moreover, we managed to find the 48.39 % of the already established OLP-related miRNAs, suggesting that at least half of the OLP-related microRNAome finely tunes few, highly interconnected hub genes. We also found other miRNAs that have not been directly linked with OLP yet but have a role in other oral diseases. For the remaining miRNAs, their role is still unknown and has to be explored. From the topological analysis, it emerges that the microRNAome generated by the selected miRNAs preserves the properties of the entire OLP-related microRNAome, being the bulk of it.

Even with the limitations of any theoretical ab initio analysis, this study can foster further research in the field of the molecular biology and genomics of oral diseases, suggesting targeted biomolecular experimentation, focused on the leader genes and their miRNAs, and therefore simpler to be analysed than mass scale molecular genomics. Moreover, it may suggest new potential risk factors and therapeutic targets.

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Authors and Affiliations

  1. Department of Experimental Medicine (DIMES), Nanobiotechnology and Biophysics Laboratories (NBL), University of Genoa, Via Antonio Pastore 3, 16132, Genoa, Italy

    Nicola Luigi Bragazzi & Claudio Nicolini

  2. Nanoworld Institute Fondazione EL.B.A Nicolini (FEN), Pradalunga, Largo Redaelli 7, Bergamo, Italy

    Claudio Nicolini

Authors
  1. Nicola Luigi Bragazzi
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  2. Claudio Nicolini
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Correspondence to Nicola Luigi Bragazzi .

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Editors and Affiliations

  1. Brigham and Women’s Hospital, Boston, Massachusetts, USA

    Stephen T. Sonis, DMD, DMSc

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Bragazzi, N., Nicolini, C. (2015). Lichen Planus. In: Sonis, DMD, DMSc, S. (eds) Genomics, Personalized Medicine and Oral Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-17942-1_9

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