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Rational Approach to Finding Genes Encoding Molecular Biomarkers: Focus on Breast Cancer

Authors: Nathalie Schneider; Ellen Reed; Faddy Kamel; Enrico Ferrari; Mikhail Soloviev;

Rational Approach to Finding Genes Encoding Molecular Biomarkers: Focus on Breast Cancer

Abstract

Early detection of cancer facilitates treatment and improves patient survival. We hypothesized that molecular biomarkers of cancer could be rationally predicted based on even partial knowledge of transcriptional regulation, functional pathways and gene co-expression networks. To test our data mining approach, we focused on breast cancer, as one of the best-studied models of this disease. We were particularly interested to check whether such a ‘guilt by association’ approach would lead to pan-cancer markers generally known in the field or whether molecular subtype-specific ‘seed’ markers will yield subtype-specific extended sets of breast cancer markers. The key challenge of this investigation was to utilize a small number of well-characterized, largely intracellular, breast cancer-related proteins to uncover similarly regulated and functionally related genes and proteins with the view to predicting a much-expanded range of disease markers, especially that of extracellular molecular markers, potentially suitable for the early non-invasive detection of the disease. We selected 23 previously characterized proteins specific to three major molecular subtypes of breast cancer and analyzed their established transcription factor networks, their known metabolic and functional pathways and the existing experimentally derived protein co-expression data. Having started with largely intracellular and transmembrane marker ‘seeds’ we predicted the existence of as many as 150 novel biomarker genes to be associated with the selected three major molecular sub-types of breast cancer all coding for extracellularly targeted or secreted proteins and therefore being potentially most suitable for molecular diagnosis of the disease. Of the 150 such predicted protein markers, 114 were predicted to be linked through the combination of regulatory networks to basal breast cancer, 48 to luminal and 7 to Her2-positive breast cancer. The reported approach to mining molecular markers is not limited to breast cancer and therefore offers a widely applicable strategy of biomarker mining.

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Keywords

570, 610, C400 - Genetics, Breast Neoplasms, molecular biomarkers, Article, transcriptomics, transcription factors, C400 Genetics, gene expression, Biomarkers, Tumor, Humans, transcription factors; biological pathways; gene expression; microarrays; transcriptomics; molecular biomarkers, Female, Breast, biological pathways, microarrays, Early Detection of Cancer, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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gold
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Cancer Research