Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome.

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome.
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DOI:
10.3390/cancers13051109
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发表时间:
2021-03-05
期刊:
影响因子:
5.2
通讯作者:
Leslie KK
Leslie KK
中科院分区:
医学2区
文献类型:
--
作者:
Gonzalez-Bosquet J;Pedra-Nobre S;Devor EJ;Thiel KW;Goodheart MJ;Bender DP;Leslie KK

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微生物存在于所有人体组织中。其中一些与癌症的形成有关。在我们的研究中,我们发现细菌、古生菌和病毒在女性生殖道上部的基因表达,这种表达与卵巢癌和子宫内膜癌有关。我们还发现,这些微生物的表达可能参与了感染和癌症形成的调控机制。与这些微生物相关的一些过程可能会影响癌症的异质性,并成为癌症治疗的潜在靶点。细菌、古生菌和病毒与许多人类癌症有关。到目前为止,还没有评估转录中的微生物组变异与上女性生殖道癌风险的关系。我们的目的是评估不同妇科癌症和正常输卵管之间细菌、古生菌和病毒转录本(BAVT)表达的差异。在这项病例对照研究中,我们对12例正常输卵管、112例浆液性卵巢癌(HGSC)和62例子宫内膜样癌(EEC)进行了RNA测序。我们使用离心机算法将结果转录物分类为四个索引:细菌、古生菌、病毒和人类基因组。然后,我们比较了正常样本、HGSC和EEC中BAVT的表达。T检验用于单变量比较(对多重比较进行校正),套索用于多变量建模。为了验证,我们对正常输卵管进行了DNA测序,并与TCGA数据库中的HGSC和EEC BAVT进行了比较。对有意义的BAVT的功能进行通径分析。我们的结果表明,BAVT在不同的妇科癌症中的表达水平不同。最后,我们将其中一些BAVT映射到人类基因组。根据途径富集化分析,大量的图谱位置靠近调控基因和长的非编码RNA。BAVT可能会影响妇科癌症的风险,并可能成为癌症治疗的潜在靶点。
Microorganisms are found in all human tissues. Some of them are responsible for cancer formation. In our study we found gene expression from bacteria, archaea, and viruses in the upper female genital tract and this expression was associated with ovarian and endometrial cancer. We also found that the expression from these organisms may be involved in regulatory mechanisms of infection and cancer formation. Some of the processes associated with these organisms may affect cancer heterogeneity and be potential targets for cancer therapy. Bacteria, archaea, and viruses are associated with numerous human cancers. To date, microbiome variations in transcription have not been evaluated relative to upper female genital tract cancer risk. Our aim was to assess differences in bacterial, archaea, and viral transcript (BAVT) expression between different gynecological cancers and normal fallopian tubes. In this case-control study we performed RNA sequencing on 12 normal tubes, 112 serous ovarian cancers (HGSC) and 62 endometrioid endometrial cancers (EEC). We used the centrifuge algorithm to classify resultant transcripts into four indexes: bacterial, archaea, viral, and human genomes. We then compared BAVT expression from normal samples, HGSC and EEC. T-test was used for univariate comparisons (correcting for multiple comparison) and lasso for multivariate modelling. For validation we performed DNA sequencing of normal tubes in comparison to HGSC and EEC BAVTs in the TCGA database. Pathway analyses were carried out to evaluate the function of significant BAVTs. Our results show that BAVT expression levels vary between different gynecological cancers. Finally, we mapped some of these BAVTs to the human genome. Numerous map locations were close to regulatory genes and long non-coding RNAs based on the pathway enrichment analysis. BAVTs may affect gynecological cancer risk and may be part of potential targets for cancer therapy.
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