Abstract
BackgroundWith the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA) program to identify potential blood-based markers for six common human cancer types.Methodology/Principal FindingsIn the Oncomine platform, the genes overexpressed in cancer tissues relative to their corresponding normal tissues were filtered by Gene Ontology keywords, with the extracellular environment stipulated and a corrected Q value (false discovery rate) cut-off implemented. The identified genes were imported to the IPA biomarker module to separate out those genes encoding putative secreted or cell-surface proteins as blood-borne (blood/serum/plasma) cancer markers. The filtered potential indicators were ranked and prioritized according to normalized absolute Student t values. The retrieval of numerous marker genes that are already clinically useful or under active investigation confirmed the effectiveness of our mining strategy. To identify the biomarkers that are unique for each cancer type, the upregulated marker genes that are in common between each two tumor types across the six human tumors were also analyzed by the IPA biomarker comparison function.Conclusion/SignificanceThe upregulated marker genes shared among the six cancer types may serve as a molecular tool to complement histopathologic examination, and the combination of the commonly upregulated and unique biomarkers may serve as differentiating markers for a specific cancer. This approach will be increasingly useful to discover diagnostic signatures as the mass of microarray data continues to grow in the ‘omics’ era.
Highlights
There is a continued need for the discovery of specific blood biomarkers to aid in the noninvasive detection of cancer and the monitoring of the effectiveness of cancer therapy [1,2,3]
The general mining strategy for biomarker discovery reported here is flexible in nature
Our primary interest is to identify markers for human cancer, we believe that this mining strategy can be broadly applied to identify markers for most other types of diseases
Summary
There is a continued need for the discovery of specific blood biomarkers to aid in the noninvasive detection of cancer and the monitoring of the effectiveness of cancer therapy [1,2,3]. In pace with the post-genomic era, advanced technologies including genomic analysis and proteomics have facilitated the discovery of effective cancer biomarkers [4,5,6,7]. This paper proposes and presents a biologist friendly and effective microarray-based mining method that facilitates such biomarker discovery. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA) program to identify potential blood-based markers for six common human cancer types
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