Bioinformatics Analysis to Identify the Relationship Between Human Papillomavirus-associated Cervical Cancer, Toll-like Receptors and Exomes: A Genetic Epidemiology Study

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2024 Aug 29

PMID 39208235

Authors

Fabiana de Campos Gomes

Deizyane Dos Reis Galhardo

Aline Carvalho Goncalves Navegante

Gabriela Sepeda Dos Santos

Helana Augusta Andrade Leal Dias

Jose Ribamar Leal Dias Junior

Marie Esther Pierre

Marlucia Oliveira Luz

Joao Simao de Melo Neto

Affiliations

Soon will be listed here.

Abstract

Introduction: 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.

Materials And Methods: 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.

Results: 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]).

Conclusion: 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.

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