Combining tissue transcriptomics and urine metabolomics for breast cancer biomarker identification.
BACKGROUND
For the early detection of cancer, highly sensitive and specific biomarkers are needed. Particularly, biomarkers in bio-fluids are relatively more useful because those can be used for non-biopsy tests. Although the altered metabolic activities of cancer cells have been observed in many studies, little is known about metabolic biomarkers for cancer screening. In this study, a systematic method is proposed for identifying metabolic biomarkers in urine samples by selecting candidate biomarkers from altered genome-wide gene expression signatures of cancer cells. Biomarkers identified by the present study have increased coherence and robustness because the significances of biomarkers are validated in both gene expression profiles and metabolic profiles.


RESULTS
The proposed method was applied to the gene expression profiles and urine samples of 50 breast cancer patients and 50 normal persons. Nine altered metabolic pathways were identified from the breast cancer gene expression signatures. Among these altered metabolic pathways, four metabolic biomarkers (Homovanillate, 4-hydroxyphenylacetate, 5-hydroxyindoleacetate and urea) were identified to be different in cancer and normal subjects (p <0.05). In the case of the predictive performance, the identified biomarkers achieved area under the ROC curve values of 0.75, 0.79 and 0.79, according to a linear discriminate analysis, a random forest classifier and on a support vector machine, respectively. Finally, biomarkers which showed consistent significance in pathways' gene expression as well as urine samples were identified.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Nam
Hojung
H
Department of Bio and Brain Engineering, KAIST, 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-701, Korea.
Chung
Bong Chul
BC
Kim
Younghoon
Y
Lee
KiYoung
K
Lee
Doheon
D
D014408:Biomarkers, Tumor / Q000378:metabolism / Q000652:urine*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006719:Homovanillic Acid / Q000378:metabolism / Q000652:urine; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism / Q000652:urine; D055432:Metabolomics / Q000379:methods*; D010648:Phenylacetates / Q000378:metabolism / Q000652:urine; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D014508:Urea / Q000378:metabolism / Q000652:urine
D014408:Biomarkers, Tumor; D010648:Phenylacetates; C026246:4-hydroxyphenylacetate; D006897:Hydroxyindoleacetic Acid; D014508:Urea; D006719:Homovanillic Acid