Integrative genomic data mining for discovery of potential blood-borne biomarkers for early diagnosis of cancer.
BACKGROUND
With 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.


RESULTS
In 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.


CONCLUSIONS
The 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.
Yang
Yongliang
Y
Department of Radiology, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
Pospisil
Pavel
P
Iyer
Lakshmanan K
LK
Adelstein
S James
SJ
Kassis
Amin I
AI
D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D003110:Colonic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D030541:Databases, Genetic; D042241:Early Diagnosis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D009360:Neoplastic Cells, Circulating; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins