Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women
Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from th...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2018-09-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2018.00307/full |
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doaj-7929087bf0ed4c788a6c7611f0c358d0 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaojing Zheng Catherine M. O'Connell Wujuan Zhong Taylor B. Poston Harold C. Wiesenfeld Harold C. Wiesenfeld Sharon L. Hillier Sharon L. Hillier Maria Trent Charlotte Gaydos George Tseng Brandie D. Taylor Toni Darville |
spellingShingle |
Xiaojing Zheng Catherine M. O'Connell Wujuan Zhong Taylor B. Poston Harold C. Wiesenfeld Harold C. Wiesenfeld Sharon L. Hillier Sharon L. Hillier Maria Trent Charlotte Gaydos George Tseng Brandie D. Taylor Toni Darville Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women Frontiers in Cellular and Infection Microbiology biomarker mRNA Chlamydia gonorrhea pelvic inflammatory disease |
author_facet |
Xiaojing Zheng Catherine M. O'Connell Wujuan Zhong Taylor B. Poston Harold C. Wiesenfeld Harold C. Wiesenfeld Sharon L. Hillier Sharon L. Hillier Maria Trent Charlotte Gaydos George Tseng Brandie D. Taylor Toni Darville |
author_sort |
Xiaojing Zheng |
title |
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women |
title_short |
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women |
title_full |
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women |
title_fullStr |
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women |
title_full_unstemmed |
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women |
title_sort |
gene expression signatures can aid diagnosis of sexually transmitted infection-induced endometritis in women |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2018-09-01 |
description |
Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases. |
topic |
biomarker mRNA Chlamydia gonorrhea pelvic inflammatory disease |
url |
https://www.frontiersin.org/article/10.3389/fcimb.2018.00307/full |
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doaj-7929087bf0ed4c788a6c7611f0c358d02020-11-24T23:53:25ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-09-01810.3389/fcimb.2018.00307410299Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in WomenXiaojing Zheng0Catherine M. O'Connell1Wujuan Zhong2Taylor B. Poston3Harold C. Wiesenfeld4Harold C. Wiesenfeld5Sharon L. Hillier6Sharon L. Hillier7Maria Trent8Charlotte Gaydos9George Tseng10Brandie D. Taylor11Toni Darville12Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United StatesSection on Adolescent Medicine, Department of Pediatrics, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDivision of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Epidemiology and Biostatistics, Texas A&M University, College Station, TX, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesSexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases.https://www.frontiersin.org/article/10.3389/fcimb.2018.00307/fullbiomarkermRNAChlamydiagonorrheapelvic inflammatory disease |