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. 2010 Nov 28:5:129-38.
doi: 10.4137/BMI.S6184.

Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer

Sun Tian  1 , Paul Roepman, Laura J Van't Veer, Rene Bernards, Femke de Snoo, Annuska M Glas
Affiliations

Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer

Sun Tian et al. Biomark Insights. .

Abstract

Background: MammaPrint was developed as a diagnostic tool to predict risk of breast cancer metastasis using the expression of 70 genes. To better understand the tumor biology assessed by MammaPrint, we interpreted the biological functions of the 70-genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg.

Results: We used a bottom-up system biology approach to elucidate how the cellular processes reflected by the 70-genes work together to regulate tumor activities and progression. The biological functions of the genes were analyzed using literature research and several bioinformatics tools. Protein-protein interaction network analyses indicated that the 70-genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis, and cover the six well-defined hallmarks of cancer, reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis-related biological activities.

Conclusion: Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer-related biology. This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis.

Keywords: bioinformatics; breast cancer; functional annotation; gene signature; tumor biology.

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Figures

Figure 1.
Figure 1.
Depicted is how the genes in 70-gene tumor expression profile are involved in the six well-defined hallmarks of cancer, in tumor progression and metastasis related biological processes, as well as epithelial-mesenchymal transition. Adapted from Cell, 100, Hanahan D, Weinberg RA., The Hallmarks of Cancer, 57–70, Copyright (2000) with permission from Elsevier.
Figure 2.
Figure 2.
Protein-protein interaction network analyses indicate that the 70 genes form highly interconnected networks centered on known cancer-related transcription regulators such as TP53, RB1, MYC, JUN and CDKN2A (highlighted in orange). This network indicated that the expression levels of 70 genes are likely regulated by these key tumorigenesis related transcription regulators. The data was analyzed using Ingenuity Pathways Analysis (www.ingenuity.com).
See this image and copyright information in PMC

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