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

Abstract

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.

The Role of Microbiota in the Immunopathogenesis of Endometrial Cancer

“…Gonzalez-Bosquet et al in 2021, compared the microbiome of the female upper genital tract, in the environment of endometrial and ovarian cancer, with control samples (fallopian tubes) [ 63 ]. They measured the differences in bacterial, archaea, and viral transcripts (BAVT) between high-grade serum carcinoma (HGSC) and endometrial carcinoma (EEC), and found 93 BAVTs different in expression between the two types of gynecological tumors, of which 7 significant differences were noted: Salinibacter ruber , Bacillus tropicus , Pusillimonas sp.…”

“…They measured the differences in bacterial, archaea, and viral transcripts (BAVT) between high-grade serum carcinoma (HGSC) and endometrial carcinoma (EEC), and found 93 BAVTs different in expression between the two types of gynecological tumors, of which 7 significant differences were noted: Salinibacter ruber , Bacillus tropicus , Pusillimonas sp. ye3, Riemerella anatipestifer , Nostocales cyanobacterium HT-58-2, Orgyia pseudotsugata, and Corynebacterium pseudotuberculosis [ 63 ]. Nevertheless, in the controls, these BAVT species were the most abundant, while in the EEC samples—and even more so in the HGSC samples—BAVT expression was lower.…”

“…Nevertheless, in the controls, these BAVT species were the most abundant, while in the EEC samples—and even more so in the HGSC samples—BAVT expression was lower. These results may lead us to discover that BAVT expression is derived from genomic material embedded in the human genome that is associated with infectious and neoplastic signaling pathways [ 63 ].…”

Gut and Endometrial Microbiome Dysbiosis: A New Emergent Risk Factor for Endometrial Cancer

“…Gonzalez-Bosquet et al also investigated the origins of these BAVTs, and they saw some human loci that harbour genetic material from these microorganisms; more exactly BAVTs were located within or close to genes or lncRNAS [ 38 ].…”

Microbial Communities in Gynecological Cancers and Their Association with Tumor Somatic Variation

“…The Human Microbiome Project Consortium [ 9 , 10 ], has studied the human microbiome, including the normal microbiome of the vaginal environment. Additionally, there are a few studies about the microbiome in the upper genital tract and its association with gynecological (uterine and ovarian) cancers [ 11 , 12 ]. However, very little is known about potential mechanisms associated with malignant transformation in microbiome-associated gynecological cancer, except for HPV-induced cervical cancer [ 6 , 7 ].…”