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

PeerJ

article

Khiem Chi Lam¹  Dariia Vyshenska¹  Jialu Hu¹  Richard Rosario Rodrigues¹  Anja Nilsen⁴  Ryszard A. Zielke¹  Nicholas Samuel Brown¹  Eva-Katrine Aarnes⁴  Aleksandra E. Sikora¹  Natalia Shulzhenko⁵  Heidi Lyng⁴  Andrey Morgun¹ 

[1] College of Pharmacy, Oregon State University;Center for Cancer Research, National Cancer Institute;School of Computer Science, Northwestern Polytechnical University;Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital;Carlson College of Veterinary Medicine, Oregon State University

关键词: Transkingdom network;    Microbiome;    Prevotella bivia;    LAMP3;    Cervical cancer;   

DOI  :  10.7717/peerj.5590

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY