Posted Tue, Nov, 26,2013
Published today in Cancer Informatics is a new original research article by Mads Thomassen, Qihua Tan, Mark Burton and Torben A. Kruse. Read more about this paper below:
Title
Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer
Abstract
Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ between the subgroups are less well characterized. The molecular subtypes are associated with different risk of metastatic recurrence of the disease. Nevertheless, the performance of these overall patterns to predict outcome is far from optimal, suggesting that biological mechanisms that extend beyond the subgroups impact metastasis.
Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified comprehensive mechanistic differences between the subgroups. Furthermore, the same approach was used to investigate mechanisms related to metastasis within the subgroups. A striking finding is that the molecular subtypes account for the majority of biological mechanisms associated with metastasis. However, some mechanisms, aside from the subtypes, were identified in a training set of 1,239 tumors and confirmed by survival analysis in two independent validation datasets from the same type of platform and consisting of very comparable node-negative patients that did not receive adjuvant medical therapy. The results show that high expression of 5q14 genes and low levels of TNFR2 pathway genes were associated with poor survival in basal-like cancers. Furthermore, low expression of 5q33 genes and interleukin-12 pathway genes were associated with poor outcome exclusively in ERBB2-like tumors.
Conclusion: The identified regions, genes, and pathways may be potential drug targets in future individualized treatment strategies.
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Published This Week (5th - 9th October)Thu 08 Oct, 2015
Biomarker Insights Paper Endorsed by Editor in ChiefWed 07 Oct, 2015
Interview with Professor Jamie DaviesIt is an absolute pleasure serving as a peer reviewer for Libertas Academia. The review process was efficient and easy to navigate. I am looking forward to peer reviewing additional articles in the future.
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