Bioinformatics analysis to identify the relationship between human papillomavirus-associated cervical cancer, toll-like receptors and exomes: A genetic epidemiology study

Genetic variants may influence Toll-like receptor (TLR) signaling in the immune response to human papillomavirus (HPV) infection and lead to cervical cancer. In this study, we investigated the pattern of TLR expression in the transcriptome of HPV-positive and HPV-negative cervical cancer samples and...

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Published in:	PloS one Vol. 19; no. 8; p. e0305760
Main Authors:	Gomes, Fabiana de Campos, Galhardo, Deizyane Dos Reis, Navegante, Aline Carvalho Gonçalves, Santos, Gabriela Sepêda Dos, Dias, Helana Augusta Andrade Leal, Dias Júnior, José Ribamar Leal, Pierre, Marie Esther, Luz, Marlucia Oliveira, de Melo Neto, João Simão
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 29-08-2024 Public Library of Science (PLoS)
Subjects:	Adult Analysis Bioinformatics Biology and Life Sciences Boolean Cancer Care and treatment Cervical cancer Clinical significance Complications and side effects Computational biology Computational Biology - methods Data processing Epidemiology Female Gene expression Genetic aspects Genetic diversity Genetic variance Genomes Head & neck cancer Human papillomavirus Human Papillomavirus Viruses Human subjects Humans Immune response Immune system Infections Medicine and Health Sciences Middle Aged Minority & ethnic groups Papillomaviridae - genetics Papillomavirus infections Papillomavirus Infections - genetics Papillomavirus Infections - virology Pathogens People and Places Population genetics Population studies Populations Prevention Proteins Risk factors Statistical analysis TLR1 protein TLR3 protein TLR4 protein TLR7 protein Toll-like receptors Toll-Like Receptors - genetics Transcriptomes Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - virology Brazil United States > US
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Summary:	Genetic variants may influence Toll-like receptor (TLR) signaling in the immune response to human papillomavirus (HPV) infection and lead to cervical cancer. In this study, we investigated the pattern of TLR expression in the transcriptome of HPV-positive and HPV-negative cervical cancer samples and looked for variants potentially related to TLR gene alterations in exomes from different populations. A cervical tissue sample from 28 women, which was obtained from the Gene Expression Omnibus database, was used to examine TLR gene expression. Subsequently, the transcripts related to the TLRs that showed significant gene expression were queried in the Genome Aggregation Database to search for variants in more than 5,728 exomes from different ethnicities. Cancer and HPV were found to be associated (p<0.0001). TLR1(p = 0.001), TLR3(p = 0.004), TLR4(221060_s_at)(p = 0.001), TLR7(p = 0.001;p = 0.047), TLR8(p = 0.002) and TLR10(p = 0.008) were negatively regulated, while TLR4(1552798_at)(p<0.0001) and TLR6(p = 0.019) were positively regulated in HPV-positive patients (p<0.05). The clinical significance of the variants was statistically significant for TLR1, TLR3, TLR6 and TLR8 in association with ethnicity. Genetic variants in different TLRs have been found in various ethnic populations. Variants of the TLR gene were of the following types: TLR1(5_prime_UTR), TLR4(start_lost), TLR8(synonymous;missense) and TLR10(3_prime_UTR). The "missense" variant was found to have a risk of its clinical significance being pathogenic in South Asian populations (OR = 56,820[95%CI:40,206,80,299]). The results of this study suggest that the variants found in the transcriptomes of different populations may lead to impairment of the functional aspect of TLRs that show significant gene expression in cervical cancer samples caused by HPV.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0305760