当前位置： SCI文献检索 > BMC Medicine期刊下所有文献 > Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data.

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data.

Abstract：

BACKGROUND:Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies. METHODS:On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data. RESULTS:Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with 'low cancer-risk' characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring 'high cancer-risk" characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest 'high cancer- risk' cluster were different than those contributing to the classifiers for the 'low cancer-risk' clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different. CONCLUSIONS:The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs.

journal_name

BMC Med

journal_title

BMC medicine

authors

Emmert-Streib F,Abogunrin F,de Matos Simoes R,Duggan B,Ruddock MW,Reid CN,Roddy O,White L,O'Kane HF,O'Rourke D,Anderson NH,Nambirajan T,Williamson KE

doi

10.1186/1741-7015-11-12

subject

Has Abstract

pub_date

2013-01-17 00:00:00

pages

issn

1741-7015

pii

1741-7015-11-12

journal_volume

pub_type

杂志文章

在线工具

Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data.