Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer
Abstract
Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profilemore »
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1581861
- Alternate Identifier(s):
- OSTI ID: 1606967
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Published Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Name: PLoS ONE Journal Volume: 15 Journal Issue: 1; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Cancer detection and diagnosis; Ascites; Machine learning; Diagnostic medicine; Clostridium; Microbiome; Surgical oncology; Ovarian cancer
Citation Formats
Miao, Ruizhong, Badger, Taylor C., Groesch, Kathleen, Diaz-Sylvester, Paula L., Wilson, Teresa, Ghareeb, Allen, Martin, Jongjin Anne, Cregger, Melissa, Welge, Michael, Bushell, Colleen, Auvil, Loretta, Zhu, Ruoqing, Brard, Laurent, Braundmeier-Fleming, Andrea, and Laganà, ed., Antonio Simone. Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer. United States: N. p., 2020.
Web. doi:10.1371/journal.pone.0227707.
Miao, Ruizhong, Badger, Taylor C., Groesch, Kathleen, Diaz-Sylvester, Paula L., Wilson, Teresa, Ghareeb, Allen, Martin, Jongjin Anne, Cregger, Melissa, Welge, Michael, Bushell, Colleen, Auvil, Loretta, Zhu, Ruoqing, Brard, Laurent, Braundmeier-Fleming, Andrea, & Laganà, ed., Antonio Simone. Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer. United States. https://doi.org/10.1371/journal.pone.0227707
Miao, Ruizhong, Badger, Taylor C., Groesch, Kathleen, Diaz-Sylvester, Paula L., Wilson, Teresa, Ghareeb, Allen, Martin, Jongjin Anne, Cregger, Melissa, Welge, Michael, Bushell, Colleen, Auvil, Loretta, Zhu, Ruoqing, Brard, Laurent, Braundmeier-Fleming, Andrea, and Laganà, ed., Antonio Simone. Thu .
"Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer". United States. https://doi.org/10.1371/journal.pone.0227707.
@article{osti_1581861,
title = {Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer},
author = {Miao, Ruizhong and Badger, Taylor C. and Groesch, Kathleen and Diaz-Sylvester, Paula L. and Wilson, Teresa and Ghareeb, Allen and Martin, Jongjin Anne and Cregger, Melissa and Welge, Michael and Bushell, Colleen and Auvil, Loretta and Zhu, Ruoqing and Brard, Laurent and Braundmeier-Fleming, Andrea and Laganà, ed., Antonio Simone},
abstractNote = {Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profile compared to patients with a benign mass. Using ensemble modeling and machine learning pathways, we identified 18 microbial features that were highly specific to OC pathology. Prediction analyses confirmed that inclusion of microbial features with serum tumor marker levels and control features (patient age and BMI) improved diagnostic accuracy compared to currently used models. We conclude that OC pathogenesis alters the peritoneal microbial environment and that these unique microbial features are important for accurate diagnosis of OC. Our study warrants further analyses of the importance of microbial features in regards to oncological diagnostics and possible prognostic and interventional medicine.},
doi = {10.1371/journal.pone.0227707},
journal = {PLoS ONE},
number = 1,
volume = 15,
place = {United States},
year = {2020},
month = {1}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1371/journal.pone.0227707
https://doi.org/10.1371/journal.pone.0227707
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Anaerobes and Bacterial Vaginosis in Pregnancy: Virulence Factors Contributing to Vaginal Colonisation
journal, July 2014
- Africa, Charlene; Nel, Janske; Stemmet, Megan
- International Journal of Environmental Research and Public Health, Vol. 11, Issue 7
Diagnosis of ruptured ectopic pregnancy with peritoneal lavage
journal, October 1982
- Roberts, Mont R.; Jackimczyk, Kenneth; Marx, John
- Annals of Emergency Medicine, Vol. 11, Issue 10
Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study
journal, April 2018
- Duarte, S. M. B.; Stefano, J. T.; Miele, L.
- Nutrition, Metabolism and Cardiovascular Diseases, Vol. 28, Issue 4
Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases
journal, October 2015
- Paul, Bidisha; Barnes, Stephen; Demark-Wahnefried, Wendy
- Clinical Epigenetics, Vol. 7, Issue 1
Case for a role of the microbiome in gynecologic cancers: Clinician's perspective: Role of the microbiome in gynecologic cancers
journal, August 2018
- Mert, Ismail; Walther-Antonio, Marina; Mariani, Andrea
- Journal of Obstetrics and Gynaecology Research, Vol. 44, Issue 9
Interactions Between the Intestinal Microbiome and Liver Diseases
journal, May 2014
- Schnabl, Bernd; Brenner, David A.
- Gastroenterology, Vol. 146, Issue 6
The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass
journal, February 2008
- Moore, Richard G.; Brown, Amy K.; Miller, M. Craig
- Gynecologic Oncology, Vol. 108, Issue 2
Sonographic detection of echogenic fluid and correlation with culdocentesis in the evaluation of ectopic pregnancy.
journal, May 1998
- Chen, P. C.; Sickler, G. K.; Dubinsky, T. J.
- American Journal of Roentgenology, Vol. 170, Issue 5
The Intestinal Microbiome in Early Life: Health and Disease
journal, September 2014
- Arrieta, Marie-Claire; Stiemsma, Leah T.; Amenyogbe, Nelly
- Frontiers in Immunology, Vol. 5
Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation
journal, August 2017
- Golob, Jonathan L.; Pergam, Steven A.; Srinivasan, Sujatha
- Clinical Infectious Diseases, Vol. 65, Issue 12
Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors
journal, November 2017
- Routy, Bertrand; Le Chatelier, Emmanuelle; Derosa, Lisa
- Science, Vol. 359, Issue 6371
Systematic evaluation of supervised classifiers for fecal microbiota-based prediction of colorectal cancer
journal, January 2017
- Ai, Luoyan; Tian, Haiying; Chen, Zhaofei
- Oncotarget, Vol. 8, Issue 6
The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125?
journal, September 2008
- Nossov, Vladimir; Amneus, Malaika; Su, Feng
- American Journal of Obstetrics and Gynecology, Vol. 199, Issue 3
Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass
journal, January 2011
- Partheen, Karolina; Kristjansdottir, Björg; Sundfeldt, Karin
- Journal of Gynecologic Oncology, Vol. 22, Issue 4
Gut microbiota, metabolites and host immunity
journal, May 2016
- Rooks, Michelle G.; Garrett, Wendy S.
- Nature Reviews Immunology, Vol. 16, Issue 6
The microbiome and rheumatoid arthritis
journal, August 2011
- Scher, Jose U.; Abramson, Steven B.
- Nature Reviews Rheumatology, Vol. 7, Issue 10
Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment
journal, June 2018
- Burns, Michael B.; Montassier, Emmanuel; Abrahante, Juan
- PLOS Genetics, Vol. 14, Issue 6
A Review and Tutorial of Machine Learning Methods for Microbiome Host Trait Prediction
journal, June 2019
- Zhou, Yi-Hui; Gallins, Paul
- Frontiers in Genetics, Vol. 10
Irritable bowel syndrome: a gut microbiota-related disorder?
journal, January 2017
- Bhattarai, Yogesh; Muniz Pedrogo, David A.; Kashyap, Purna C.
- American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 312, Issue 1
Regression shrinkage and selection via the lasso: a retrospective: Regression Shrinkage and Selection via the Lasso
journal, April 2011
- Tibshirani, Robert
- Journal of the Royal Statistical Society: Series B (Statistical Methodology), Vol. 73, Issue 3
Ovarian cancer screening—ultrasound; impact on ovarian cancer mortality
journal, October 2018
- Kamal, Rasha; Hamed, Soha; Mansour, Sahar
- The British Journal of Radiology, Vol. 91, Issue 1090
Imaging and Differential Diagnosis of Ovarian Cancer
journal, August 2019
- Shetty, Mahesh
- Seminars in Ultrasound, CT and MRI, Vol. 40, Issue 4
Prediction error estimation: a comparison of resampling methods
journal, May 2005
- Molinaro, A. M.; Simon, R.; Pfeiffer, R. M.
- Bioinformatics, Vol. 21, Issue 15
Blowing on Embers: Commensal Microbiota and Our Immune System
journal, July 2014
- Spasova, Darina S.; Surh, Charles D.
- Frontiers in Immunology, Vol. 5
TLR4 blockade using TAK-242 suppresses ovarian and breast cancer cells invasion through the inhibition of extracellular matrix degradation and epithelial-mesenchymal transition
journal, June 2019
- Zandi, Zahra; Kashani, Bahareh; Poursani, Ensieh M.
- European Journal of Pharmacology, Vol. 853
Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis
journal, November 2013
- Scher, Jose U.; Sczesnak, Andrew; Longman, Randy S.
- eLife, Vol. 2
Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings
journal, November 2018
- Mukherjee, Suprabhat; Joardar, Nikhilesh; Sengupta, Subhasree
- The Journal of Nutritional Biochemistry, Vol. 61
Search and clustering orders of magnitude faster than BLAST
journal, August 2010
- Edgar, Robert C.
- Bioinformatics, Vol. 26, Issue 19, p. 2460-2461
Defining dysbiosis and its influence on host immunity and disease: How changes in microbiota structure influence health
journal, June 2014
- Petersen, Charisse; Round, June L.
- Cellular Microbiology, Vol. 16, Issue 7
Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences
journal, January 2010
- Goecks, Jeremy; Nekrutenko, Anton; Taylor, James
- Genome Biology, Vol. 11, Issue 8
Variable selection using random forests
journal, October 2010
- Genuer, Robin; Poggi, Jean-Michel; Tuleau-Malot, Christine
- Pattern Recognition Letters, Vol. 31, Issue 14
Distinct Microbiotas are Associated with Ileum-Restricted and Colon-Involving Crohnʼs Disease
journal, January 2016
- Naftali, Timna; Reshef, Leah; Kovacs, Amir
- Inflammatory Bowel Diseases, Vol. 22, Issue 2
The role of the vaginal microbiome in gynaecological cancer
journal, April 2017
- Champer, M.; Wong, Am; Champer, J.
- BJOG: An International Journal of Obstetrics & Gynaecology, Vol. 125, Issue 3
CA-125 concentration in serum and peritoneal fluid in patients with endometriosis – preliminary results
journal, January 2012
- Szubert, Maria; Suzin, Jacek; Wierzbowski, Tomasz
- Archives of Medical Science, Vol. 3
HE4 in the differential diagnosis of ovarian masses
journal, June 2015
- Granato, Teresa; Porpora, Maria Grazia; Longo, Flavia
- Clinica Chimica Acta, Vol. 446
The Genome of Akkermansia muciniphila, a Dedicated Intestinal Mucin Degrader, and Its Use in Exploring Intestinal Metagenomes
journal, March 2011
- van Passel, Mark W. J.; Kant, Ravi; Zoetendal, Erwin G.
- PLoS ONE, Vol. 6, Issue 3
On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other
journal, March 1947
- Mann, H. B.; Whitney, D. R.
- The Annals of Mathematical Statistics, Vol. 18, Issue 1
Dietary modulation of the microbiome affects autoinflammatory disease
journal, September 2014
- Lukens, John R.; Gurung, Prajwal; Vogel, Peter
- Nature, Vol. 516, Issue 7530
Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer
journal, March 2010
- Andersen, M. Robyn; Goff, Barbara A.; Lowe, Kimberly A.
- Gynecologic Oncology, Vol. 116, Issue 3
Unraveling a difficult diagnosis: the tricks for early recognition of ovarian cancer
journal, July 2019
- Giampaolino, Pierluigi; Della Corte, Luigi; Foreste, Virginia
- Minerva Medica, Vol. 110, Issue 4
A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis
journal, September 2013
- Machiels, Kathleen; Joossens, Marie; Sabino, João
- Gut, Vol. 63, Issue 8
Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement
journal, February 2018
- Grossman, David C.; Curry, Susan J.; Owens, Douglas K.
- JAMA, Vol. 319, Issue 6
Immune mediator expression signatures are associated with improved outcome in ovarian carcinoma
journal, March 2019
- Nakamura, Mano; Bax, Heather J.; Scotto, Daniele
- OncoImmunology, Vol. 8, Issue 6
The role of the microbiome in cancer development and therapy: Microbiome and Cancer
journal, May 2017
- Bhatt, Aadra P.; Redinbo, Matthew R.; Bultman, Scott J.
- CA: A Cancer Journal for Clinicians, Vol. 67, Issue 4
CA 125 in peritoneal fluid and serum from patients with benign gynecologic conditions and ovarian cancer
journal, February 1990
- Hunter, V. J.; Weinberg, J. B.; Haney, A. F.
- Gynecologic Oncology, Vol. 36, Issue 2
HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm
journal, February 2011
- Van Gorp, T.; Cadron, I.; Despierre, E.
- British Journal of Cancer, Vol. 104, Issue 5
The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome
journal, July 2012
- McDonald, Daniel; Clemente, Jose C.; Kuczynski, Justin
- GigaScience, Vol. 1, Issue 1
Insights into the Role of Erysipelotrichaceae in the Human Host
journal, November 2015
- Kaakoush, Nadeem O.
- Frontiers in Cellular and Infection Microbiology, Vol. 5
QIIME allows analysis of high-throughput community sequencing data
journal, April 2010
- Caporaso, J. Gregory; Kuczynski, Justin; Stombaugh, Jesse
- Nature Methods, Vol. 7, Issue 5
Galaxy: A platform for interactive large-scale genome analysis
journal, September 2005
- Giardine, B.
- Genome Research, Vol. 15, Issue 10
Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation
journal, December 2014
- Gregory, Jill C.; Buffa, Jennifer A.; Org, Elin
- Journal of Biological Chemistry, Vol. 290, Issue 9
Phylogenomics and signature proteins for the alpha Proteobacteria and its main groups
journal, January 2007
- Gupta, Radhey S.; Mok, Amy
- BMC Microbiology, Vol. 7, Issue 1
The gut microbiome, symptoms, and targeted interventions in children with cancer: a systematic review
journal, November 2017
- Bai, Jinbing; Behera, Madhusmita; Bruner, Deborah Watkins
- Supportive Care in Cancer, Vol. 26, Issue 2
Leveraging sequence-based faecal microbial community survey data to identify a composite biomarker for colorectal cancer
journal, March 2017
- Shah, Manasi S.; DeSantis, Todd Z.; Weinmaier, Thomas
- Gut, Vol. 67, Issue 5
Discovery of a Novel Seminal Fluid Microbiome and Influence of Estrogen Receptor Alpha Genetic Status
journal, March 2016
- Javurek, Angela B.; Spollen, William G.; Ali, Amber M. Mann
- Scientific Reports, Vol. 6, Issue 1
Complete genome sequence of Odoribacter splanchnicus type strain (1651/6T)
journal, April 2011
- Göker, Markus; Gronow, Sabine; Zeytun, Ahmet
- Standards in Genomic Sciences, Vol. 4, Issue 2
Microbiota: a key orchestrator of cancer therapy
journal, March 2017
- Roy, Soumen; Trinchieri, Giorgio
- Nature Reviews Cancer, Vol. 17, Issue 5
Mediterranean Diet and Health: Food Effects on Gut Microbiota and Disease Control
journal, July 2014
- Del Chierico, Federica; Vernocchi, Pamela; Dallapiccola, Bruno
- International Journal of Molecular Sciences, Vol. 15, Issue 7
Diagnostic value of derived neutrophil‐to‐lymphocyte ratio in patients with ovarian cancer
journal, January 2019
- Wu, Yang‐yang; Qin, Yuan‐yuan; Qin, Jin‐qiu
- Journal of Clinical Laboratory Analysis, Vol. 33, Issue 4
Measuring and testing dependence by correlation of distances
journal, December 2007
- Székely, Gábor J.; Rizzo, Maria L.; Bakirov, Nail K.
- The Annals of Statistics, Vol. 35, Issue 6
Regularization Paths for Generalized Linear Models via Coordinate Descent
journal, January 2010
- Friedman, Jerome; Hastie, Trevor; Tibshirani, Robert
- Journal of Statistical Software, Vol. 33, Issue 1
Immune System and DNA Repair Defects in Ovarian Cancer: Implications for Locoregional Approaches
journal, May 2019
- Farolfi, Alberto; Gurioli, Giorgia; Fugazzola, Paola
- International Journal of Molecular Sciences, Vol. 20, Issue 10
The vaginal and gastrointestinal microbiomes in gynecologic cancers: A review of applications in etiology, symptoms and treatment
journal, July 2015
- Chase, Dana; Goulder, Alison; Zenhausern, Frederic
- Gynecologic Oncology, Vol. 138, Issue 1
The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead
journal, May 2014
- Kostic, Aleksandar D.; Xavier, Ramnik J.; Gevers, Dirk
- Gastroenterology, Vol. 146, Issue 6
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
journal, March 2012
- Caporaso, J. Gregory; Lauber, Christian L.; Walters, William A.
- The ISME Journal, Vol. 6, Issue 8
Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas gingivalis , Prevotella intermedia and Prevotella nigrescens
journal, May 1998
- Aguilera, O.; Andrés, M. T.; Heath, J.
- FEMS Immunology & Medical Microbiology, Vol. 21, Issue 1
Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy
journal, October 2016
- Gomez-Arango, Luisa F.; Barrett, Helen L.; McIntyre, H. David
- Hypertension, Vol. 68, Issue 4
Feasibility and surgical outcomes of conventional and robot-assisted laparoscopy for early-stage ovarian cancer: a retrospective, multicenter analysis
journal, April 2016
- Bellia, Adriano; Vitale, Salvatore Giovanni; Laganà, Antonio Simone
- Archives of Gynecology and Obstetrics, Vol. 294, Issue 3
HE4 tumor marker concentration in neoplastic peritoneal effusion and in peritoneal fluid associated with benign gynecological diseases
journal, January 2014
- Chudecka-Głaz, Anita; Cymbaluk-Płoska, Aneta; Menkiszak, Janusz
- Journal of Ovarian Research, Vol. 7, Issue 1
Comprehensive Serum Profiling for the Discovery of Epithelial Ovarian Cancer Biomarkers
journal, December 2011
- Yip, Ping; Chen, Tzong-Hao; Seshaiah, Partha
- PLoS ONE, Vol. 6, Issue 12
Robotic Surgery in Women With Ovarian Cancer: Surgical Technique and Evidence of Clinical Outcomes
journal, March 2016
- Minig, Lucas; Padilla Iserte, Pablo; Zorrero, Cristina
- Journal of Minimally Invasive Gynecology, Vol. 23, Issue 3