Abstract PO032: Bacterial, archaea and viral transcripts (BAVT) expression in endometrial cancer

Abstract

Abstract Objectives: Microbes are found virtually everywhere, including the human body. High-throughput sequencing of microbial genome, also known as metagenomic sequencing, may help to understand interactions between human and microbial processes. In this pilot study we aimed to determine differences of bacterial, archaea and viral expression between normal fallopian tube samples and ovarian and endometrial cancer samples. Then, we assessed these differentially expressed transcripts in endometrial and ovarian cancer from TCGA data. Methods: RNA was extracted and sequenced from 62 endometrial cancers, 104 high-grade serous ovarian cancers and 12 normal tubes specimens from our Biobank repository. Sequencing was performed using the Illumina HiSeq4000 platform that sequences 150 bp paired-end transcripts. Reads were processed with Centrifuge, a novel algorithm that classifies metagenomic sequences. We built our own index to differentiate between bacterial, archaea, viral and human transcripts. Resulting number of transcripts were normalized, log transformed and compared between tubal epithelium and ovarian and endometrial cancers (t-test). Lasso regression was used to identify significant independent transcripts between samples. TCGA ovarian and endometrial samples were processed as previously, and expression of significant probes were evaluated. Results: Bacterial, archaea and viral transcripts (BAVT) were 4.7% and 3,1% of all transcriptome in tubal and ovarian cancer respectively. 266 transcripts were differentially expressed between normal tubes and ovarian and endometrial cancer, with a p<0.005. 11 bacteria and 1 virus were independently significant in the multivariate regression model. These microbes were mapped close to genome regulatory areas. In general, there were more BVAT in normal tube samples. The amount of BAVT decreased in endometrial cancer and even more in ovarian cancer, supporting this regulatory role of BAVT. BAVTs in TCGA were 0.8% of all transcriptome. Conclusions: BAVT expression is different between normal tissues and cancers in the gynecologic tract. Cancer amount of BAVT seems to decrease in malignant tissues, supporting a regulatory role of BAVT. Further studies are needed to determine the significance of BAVT amount and change of expression. Citation Format: Silvana Pedra Nobre, Nicholas Cardillo, David Bender, Michael Goodheart, Eric Devor, Jesus Gonzalez Bosquet. Bacterial, archaea and viral transcripts (BAVT) expression in endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO032.