Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian Cancer
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{"title"=>"Systematic evaluation of candidate blood markers for detecting ovarian cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Chana", "last_name"=>"Palmer", "scopus_author_id"=>"12040165700"}, {"first_name"=>"Xiaobo", "last_name"=>"Duan", "scopus_author_id"=>"36991484300"}, {"first_name"=>"Sarah", "last_name"=>"Hawley", "scopus_author_id"=>"8641105500"}, {"first_name"=>"Natalie", "last_name"=>"Scholler", "scopus_author_id"=>"6507052595"}, {"first_name"=>"Jason D.", "last_name"=>"Thorpe", "scopus_author_id"=>"24330091800"}, {"first_name"=>"Rob A.", "last_name"=>"Sahota", "scopus_author_id"=>"16053291100"}, {"first_name"=>"May Q.", "last_name"=>"Wong", "scopus_author_id"=>"57199130722"}, {"first_name"=>"Andrew", "last_name"=>"Wray", "scopus_author_id"=>"25423327800"}, {"first_name"=>"Lindsay A.", "last_name"=>"Bergan", "scopus_author_id"=>"57195268933"}, {"first_name"=>"Charles W.", "last_name"=>"Drescher", "scopus_author_id"=>"7003517876"}, {"first_name"=>"Martin W.", "last_name"=>"McIntosh", "scopus_author_id"=>"7103028985"}, {"first_name"=>"Patrick O.", "last_name"=>"Brown", "scopus_author_id"=>"35414776900"}, {"first_name"=>"Brad H.", "last_name"=>"Nelson", "scopus_author_id"=>"7402428032"}, {"first_name"=>"Nicole", "last_name"=>"Urban", "scopus_author_id"=>"7006930783"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-49949094123", "pui"=>"352197312", "doi"=>"10.1371/journal.pone.0002633", "isbn"=>"1932-6203", "sgr"=>"49949094123", "pmid"=>"18612378"}, "id"=>"02a03b5c-93e0-3c1e-8184-d7673079c36f", "abstract"=>"BACKGROUND: Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer. METHODS AND FINDINGS: We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma) samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers--MUC16, WFDC2, MSLN and MMP7--warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer. CONCLUSIONS: By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and controls as performance metrics and demonstrated the importance of stratifying analyses by histological type of ovarian cancer. Also, we discussed the limitations of studies (like this one) that use samples obtained from symptomatic women to assess potential utility in detection of disease months to years prior to clinical detection.", "link"=>"http://www.mendeley.com/research/systematic-evaluation-candidate-blood-markers-detecting-ovarian-cancer-8", "reader_count"=>6, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Nigeria"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/928124"], "description"=>"<p>Bar heights indicate the mean of the normalized values of a given marker in the specified subset of cases or controls. Error bars represent the 95% confidence interval associated with the mean. The logarithm of serum marker concentrations were normalized to standard deviations from the mean of the corresponding measurements in Healthy Controls.</p>", "links"=>[], "tags"=>["serum"], "article_id"=>598558, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Normalized_serum_marker_levels_/598558", "title"=>"Normalized serum marker levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-07-09 02:22:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/460159", "https://ndownloader.figshare.com/files/460171"], "description"=>"<div><h3>Background</h3><p>Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer.</p><h3>Methods and Findings</h3><p>We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma) samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers-MUC16, WFDC2, MSLN and MMP7-warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer.</p><h3>Conclusions</h3><p>By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and controls as performance metrics and demonstrated the importance of stratifying analyses by histological type of ovarian cancer. Also, we discussed the limitations of studies (like this one) that use samples obtained from symptomatic women to assess potential utility in detection of disease months to years prior to clinical detection.</p></div>", "links"=>[], "tags"=>["systematic", "markers", "detecting", "ovarian", "cancer"], "article_id"=>150668, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002633.s001", "https://dx.doi.org/10.1371/journal.pone.0002633.s002"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Systematic_Evaluation_of_Candidate_Blood_Markers_for_Detecting_Ovarian_Cancer/150668", "title"=>"Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-07-09 00:11:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/928406"], "description"=>"a<p>AdenoNOS = Adenocarcinoma Not Otherwise Specified</p>", "links"=>[], "tags"=>["histology", "ovarian", "cases", "serum"], "article_id"=>598842, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stage_and_histology_of_ovarian_cases_in_each_serum_set_/598842", "title"=>"Stage and histology of ovarian cases in each serum set.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:27:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/928455"], "description"=>"a)<p>Sens98 = Sensitivity at 98% specificity in discriminating cases from all controls (Healthy Controls, Surgical Benigns and Surgical Normals).</p>b)<p>Sens95 = Sensitivity at 95% specificity in discriminating cases from all controls (Healthy Controls, Surgical Benigns and Surgical Normals).</p>c)<p>AUC = Area Under (ROC) Curve for discriminating cases from all controls (Healthy Controls, Surgical Benigns and Surgical Normals).</p>d)<p>Discriminatory Dist. = Discriminatory Distance. The logarithm of serum marker concentrations were normalized to standard deviations from the mean of the corresponding measurements in Healthy Controls. Mean, SE (95% CI) = Mean, standard error, and 95% confidence intervals of difference between normalized serum marker concentration in cases and in Healthy Controls.</p>", "links"=>[], "tags"=>["oncology", "women's health", "oncology/gynecological cancers", "women's health/gynecological cancers"], "article_id"=>598887, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_marker_performance_/598887", "title"=>"Single marker performance.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:28:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/928356"], "description"=>"<p>Summary of correctly identified cases by histological type.</p>", "links"=>[], "tags"=>["cases", "histological"], "article_id"=>598792, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t005", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_correctly_identified_cases_by_histological_type_/598792", "title"=>"Summary of correctly identified cases by histological type.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:26:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/928302"], "description"=>"a)<p>Sens98 = Sensitivity at 98% specificity in discriminating cases from all controls (Healthy Controls, Surgical Benigns and Surgical Normals).</p>b)<p>AUC = Area Under (ROC) Curve for discriminating cases from all controls (Healthy Controls, Surgical Benigns and Surgical Normals).</p>c)<p>P-value for the best available two-marker combination compared to the best available three-marker combination (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002633#s4\" target=\"_blank\">Materials and Methods</a>).</p>", "links"=>[], "tags"=>["oncology", "women's health", "oncology/gynecological cancers", "women's health/gynecological cancers"], "article_id"=>598736, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combination_marker_performance_/598736", "title"=>"Combination marker performance.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:25:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/928251"], "description"=>"<p>Bead-based immunoassay reagents.</p>", "links"=>[], "tags"=>["immunoassay"], "article_id"=>598689, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t007", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bead_based_immunoassay_reagents_/598689", "title"=>"Bead-based immunoassay reagents.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:24:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/928203"], "description"=>"a)<p>All assays were conducted on serum with the exception of SPP1 which was conducted using plasma-EDTA. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002633#pone.0002633.s002\" target=\"_blank\">Table S2</a> for catalogue numbers.</p>", "links"=>[], "tags"=>["elisa"], "article_id"=>598642, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t006", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Commercial_ELISA_reagents_/598642", "title"=>"Commercial ELISA reagents.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:24:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/928502"], "description"=>"a)<p>Overlapping specimens in the Mini-Triage and Triage sets</p>b)<p>Healthy Controls: women enrolled in prospective screening trials who remained free of ovarian cancer for at least two years after serum collection.</p>c)<p>Surgical Benigns: women with surgically confirmed benign ovarian pathology.</p>d)<p>Surgical Normals: women that underwent surgery but no ovarian pathology was identified.</p>", "links"=>[], "tags"=>["cases"], "article_id"=>598943, "categories"=>["Cancer", "Medicine", "Mathematics"], "users"=>["Chana Palmer", "Xiaobo Duan", "Sarah Hawley", "Nathalie Scholler", "Jason D. Thorpe", "Rob A. Sahota", "May Q. Wong", "Andrew Wray", "Lindsay A. Bergan", "Charles W. Drescher", "Martin W. McIntosh", "Patrick O. Brown", "Brad H. Nelson", "Nicole Urban"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002633.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Marker_evaluation_pipeline_cases_and_controls_/598943", "title"=>"Marker evaluation pipeline: cases and controls.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-09 02:29:03"}

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Relative Metric

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