Postgraduate Program in Collective Health in the Amazon (PPGSCA), Federal University of Pará (UFPA), Belém, Pará, Brazil.
Faculty of Medicine CERES (FACERES), São José do Rio Preto, São Paulo, Brazil.
PLoS One. 2024 Aug 29;19(8):e0305760. doi: 10.1371/journal.pone.0305760. eCollection 2024.
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.
遗传变异可能影响 Toll 样受体 (TLR) 信号在人乳头瘤病毒 (HPV) 感染的免疫反应，并导致宫颈癌。在这项研究中，我们研究了 HPV 阳性和 HPV 阴性宫颈癌样本中转录组中 TLR 表达的模式，并寻找了外显子中可能与 TLR 基因改变相关的变体不同人群。
从基因表达综合数据库中获得了 28 名女性的宫颈组织样本，用于检查 TLR 基因表达。随后，在基因组聚合数据库中查询与 TLR 相关的转录本在不同种族的超过 5728 个外显子中搜索变体。
发现癌症和 HPV 相关（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)和 TLR10(p = 0.008)被负调节，而 TLR4(1552798_at)(p<0.0001)和 TLR6(p = 0.019)在 HPV 阳性患者中呈正调节（p<0.05）。TLR1、TLR3、TLR6 和 TLR8 与种族相关的变体的临床意义具有统计学意义。不同 TLR 中的遗传变异在不同种族人群中均有发现。TLR 基因的变体有以下类型：TLR1(5_prime_UTR)、TLR4(start_lost)、TLR8(synonymous;missense)和 TLR10(3_prime_UTR)。“错义”变体被发现具有致病性的临床意义在南亚人群中风险较高（OR = 56,820[95%CI:40,206,80,299]）。
本研究结果表明，不同人群转录组中发现的变体可能导致 HPV 引起的宫颈癌样本中 TLR 基因表达显著的 TLR 功能方面受损。
