Transkingdom network reveals bacterial players associated with cervical cancer gene expression program
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 g...
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| Format: | Article |
| Language: | English |
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PeerJ Inc.
2018-09-01
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| Series: | PeerJ |
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| Online Access: | https://peerj.com/articles/5590.pdf |
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| author | Khiem Chi Lam Dariia Vyshenska Jialu Hu Richard Rosario Rodrigues Anja Nilsen Ryszard A. Zielke Nicholas Samuel Brown Eva-Katrine Aarnes Aleksandra E. Sikora Natalia Shulzhenko Heidi Lyng Andrey Morgun |
| author_facet | Khiem Chi Lam Dariia Vyshenska Jialu Hu Richard Rosario Rodrigues Anja Nilsen Ryszard A. Zielke Nicholas Samuel Brown Eva-Katrine Aarnes Aleksandra E. Sikora Natalia Shulzhenko Heidi Lyng Andrey Morgun |
| author_sort | Khiem Chi Lam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T07:28:06Z |
| format | Article |
| id | doaj.art-4863c8884d6c408ea881cc6b60bf3c1e |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:28:06Z |
| publishDate | 2018-09-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-4863c8884d6c408ea881cc6b60bf3c1e2023-12-03T06:47:18ZengPeerJ Inc.PeerJ2167-83592018-09-016e559010.7717/peerj.5590Transkingdom network reveals bacterial players associated with cervical cancer gene expression programKhiem Chi Lam0Dariia Vyshenska1Jialu Hu2Richard Rosario Rodrigues3Anja Nilsen4Ryszard A. Zielke5Nicholas Samuel Brown6Eva-Katrine Aarnes7Aleksandra E. Sikora8Natalia Shulzhenko9Heidi Lyng10Andrey Morgun11College of Pharmacy, Oregon State University, Corvallis, OR, USACollege of Pharmacy, Oregon State University, Corvallis, OR, USACollege of Pharmacy, Oregon State University, Corvallis, OR, USACollege of Pharmacy, Oregon State University, Corvallis, OR, USAInstitute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayCollege of Pharmacy, Oregon State University, Corvallis, OR, USACollege of Pharmacy, Oregon State University, Corvallis, OR, USAInstitute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayCollege of Pharmacy, Oregon State University, Corvallis, OR, USACarlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USAInstitute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayCollege of Pharmacy, Oregon State University, Corvallis, OR, USACervical 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.https://peerj.com/articles/5590.pdfTranskingdom networkMicrobiomePrevotella biviaLAMP3Cervical cancer |
| spellingShingle | Khiem Chi Lam Dariia Vyshenska Jialu Hu Richard Rosario Rodrigues Anja Nilsen Ryszard A. Zielke Nicholas Samuel Brown Eva-Katrine Aarnes Aleksandra E. Sikora Natalia Shulzhenko Heidi Lyng Andrey Morgun Transkingdom network reveals bacterial players associated with cervical cancer gene expression program PeerJ Transkingdom network Microbiome Prevotella bivia LAMP3 Cervical cancer |
| title | Transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| title_full | Transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| title_fullStr | Transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| title_full_unstemmed | Transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| title_short | Transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| title_sort | transkingdom network reveals bacterial players associated with cervical cancer gene expression program |
| topic | Transkingdom network Microbiome Prevotella bivia LAMP3 Cervical cancer |
| url | https://peerj.com/articles/5590.pdf |
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