Transkingdom network reveals bacterial players associated with cervical cancer gene expression program.

Autor:	Lam KC; College of Pharmacy, Oregon State University, Corvallis, OR, USA.; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Vyshenska D; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Hu J; College of Pharmacy, Oregon State University, Corvallis, OR, USA.; School of Computer Science, Northwestern Polytechnical University, Xi'an, China., Rodrigues RR; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Nilsen A; Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Zielke RA; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Brown NS; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Aarnes EK; Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Sikora AE; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Shulzhenko N; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA., Lyng H; Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Morgun A; College of Pharmacy, Oregon State University, Corvallis, OR, USA.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2018 Sep 19; Vol. 6, pp. e5590. Date of Electronic Publication: 2018 Sep 19 (Print Publication: 2018).
DOI:	10.7717/peerj.5590
Abstrakt:	Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause the disease. Chromosomal amplifications have been identified as a source of upregulation for cervical cancer driver genes but cannot fully explain increased expression of immune genes in invasive carcinoma. Insight into additional factors that may tip the balance from immune tolerance of HPV to the elimination of the virus may lead to better diagnosis markers. We investigated whether microbiota affect molecular pathways in cervical carcinogenesis by performing microbiome analysis via sequencing 16S rRNA in tumor biopsies from 121 patients. While we detected a large number of intra-tumor taxa (289 operational taxonomic units (OTUs)), we focused on the 38 most abundantly represented microbes. To search for microbes and host genes potentially involved in the interaction, we reconstructed a transkingdom network by integrating a previously discovered cervical cancer gene expression network with our bacterial co-abundance network and employed bipartite betweenness centrality. The top ranked microbes were represented by the families Bacillaceae , Halobacteriaceae , and Prevotellaceae . While we could not define the first two families to the species level, Prevotellaceae was assigned to Prevotella bivia . By co-culturing a cervical cancer cell line with P. bivia , we confirmed that three out of the ten top predicted genes in the transkingdom network (lysosomal associated membrane protein 3 (LAMP3), STAT1, TAP1), all regulators of immunological pathways, were upregulated by this microorganism. Therefore, we propose that intra-tumor microbiota may contribute to cervical carcinogenesis through the induction of immune response drivers, including the well-known cancer gene LAMP3. Competing Interests: The authors declare that they have no competing interests.
Databáze:	MEDLINE
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