背景:在人乳头瘤病毒(HPV)感染的免疫反应中,遗传变异可能会影响Toll样受体(TLR)信号传导并导致宫颈癌。在这项研究中,我们调查了HPV阳性和HPV阴性宫颈癌样本的转录组中TLR表达模式,并在不同人群的外显子组中寻找可能与TLR基因改变相关的变异.
方法:来自28名女性的宫颈组织样本,从基因表达综合数据库获得,用于检查TLR基因表达。随后,在基因组聚集数据库中查询与显示显著基因表达的TLR相关的转录本,以在来自不同种族的5,728多个外显子组中搜索变体.
结果: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)负调控,而TLR4(1552798_at)(p<0.0001)和TLR6(p=0.019)在HPV阳性患者中呈正调控(p<0.05)。这些变体的临床意义对于TLR1、TLR3、TLR6和TLR8与种族相关具有统计学意义。在不同种族人群中发现了不同TLR的遗传变异。TLR基因的变异体有以下几种类型:TLR1(5_prime_UTR),TLR4(start_lost),TLR8(同义词;错义)和TLR10(3_prime_UTR)。发现“错义”变体在南亚人群中具有致病性的临床意义的风险(OR=56,820[95CI:40,206,80,299])。
结论:这项研究的结果表明,在不同人群的转录组中发现的变异可能导致在HPV引起的宫颈癌样本中显示显著基因表达的TLR的功能方面受损。
BACKGROUND: 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.
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]).
CONCLUSIONS: 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.