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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 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.

SUBMITTER: Miao R

PROVIDER: S-EPMC6952086 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer.

Miao Ruizhong R Badger Taylor C TC Groesch Kathleen K Diaz-Sylvester Paula L PL Wilson Teresa T Ghareeb Allen A Martin Jongjin Anne JA Cregger Melissa M Welge Michael M Bushell Colleen C Auvil Loretta L Zhu Ruoqing R Brard Laurent L Braundmeier-Fleming Andrea A

PloS one 20200109 1

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 b ...[more]

PMID: 31917801

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Project description:To evaluate the use of molecularly targeted microbubbles (MBs) and ultrasonography (US) in the noninvasive assessment of the level of expression of three angiogenic markers, α(v)β(3) integrin, endoglin, and vascular endothelial growth factor receptor (VEGFR) 2, on tumor vascular endothelial cells in vivo during tumor growth.All procedures using laboratory animals were approved by the Institutional Administrative Panel on Laboratory Animal Care. Binding specificity of three types of targeted MBs (MB(Integrin), MB(Endoglin), MB(VEGFR2)) was tested in cell culture under flow shear stress conditions. In vivo targeted contrast material-enhanced US imaging signal using the three MB types was measured at three tumor stages (small, medium, large) in three subcutaneous cancer xenografts (breast, ovarian, pancreatic cancer) in mice (n = 54). In vivo US imaging signal was correlated with ex vivo angiogenic marker expression. Significant differences were evaluated by using the Student t, analysis of variance, Wilcoxon, and Tukey Honest Significant Difference tests.Cell attachment of all three MB types was significantly (P = .016) higher compared with control MBs, and this attachment could be significantly (P = .026) decreased by blocking antibodies. Angiogenic marker-expressing cells bound significantly (P = .003) more targeted MBs than negative control cells, and MB attachment significantly (P < .001) correlated with marker expression levels on cells (ρ = 0.87). In early stage breast and ovarian cancers, in vivo targeted contrast-enhanced US demonstrated significantly (P ≤ .04) higher endoglin expression than both α(v)β(3) integrin and VEGFR2 expression, whereas in early stage pancreatic cancer, marker expressions were not significantly different (P ≥ .07). There was good correlation (ρ ≥ 0.63; P ≤ .05) between in vivo targeted contrast-enhanced US imaging signals using the three MB types and ex vivo immunoblotting results regarding expression levels of the three angiogenic markers. Immunofluorescence confirmed expression of α(v)β(3) integrin, endoglin, and VEGFR2 on tumor vascular endothelial cells.Targeted contrast-enhanced US imaging allows noninvasive in vivo assessment of the expression levels of α(v)β(3) integrin, endoglin, and VEGFR2, which vary during tumor growth in subcutaneous cancer xenografts.

Dataset Information

Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer.

Publications

Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer.

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