Identification of a robust gene signature that predicts breast cancer outcome in independent data sets

Korkola, James E.; Blaveri, Ekaterini; DeVries, Sandy; Moore, Dan H.; Hwang, E. Shelley; Chen, Yunn Yi; Estep, Anne L.; Chew, Karen; Jensen, Ronald H.; Waldman, Frederic M.

doi:10.1186/1471-2407-7-61

Cited by 38 publications

(29 citation statements)

References 32 publications

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“…To test the relationship between clinical outcome and the expression of genes highly correlated with h4, four independent gene profiling data sets were analyzed (19,21,22,30). This analysis is based on the hypothesis that genes whose expression correlates significantly may function in common mechanisms to affect tumor behavior.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

Simin²,

Khan³

et al. 2008

Clinical Cancer Research

114

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Purpose: The h4 integrin has been implicated in functions associated with the genesis and progression of carcinomas based on data obtained from cell lines and mouse models. Data on its expression and relevance to human carcinomas, however, are relatively scant. The aim of this study was to assess its expression and prognostic significance in human breast carcinomas. Experimental Design: We integrated data on h4 expression from multiple gene profiling studies of breast tumors of known clinical outcome with immunohistochemical analysis of 105 breast carcinomas, and we identified genes whose expression correlates with that of h4. Results: The expression of both h4 mRNA and protein is not homogeneous in breast cancer and it associates most significantly with the ''basal-like'' subtype of breast tumors (P = 0.008). No association between h4 and HER2 expression was evident from either gene profiling or immunohistochemical analysis. To gain insight into the relevance of h4 expression to human breast carcinomas, we generated a 65-gene ''h4 signature'' based on integration of four published gene profiling studies that included the top 0.1% of genes that correlated with h4, either positively or negatively. This h4 signature predicted decreased time to tumor recurrence and survival of patients when applied to four data sets including two independent ones. Conclusions: These observations indicate that h4 expression in human breast cancer is restricted and associated with basal-like cancers, and they support the hypothesis that h4 may function in concert with a discrete set of proteins to facilitate the aggressive behavior of a subset of tumors.

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Section: Resultsmentioning

confidence: 99%

Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

Simin²,

Khan³

et al. 2008

Clinical Cancer Research

114

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show abstract

“…This approach has been applied to diseases of unknown cause to create new hypotheses relating to disease pathogenesis (7,8) and is shown to have prognostic (9) and diagnostic applications (10,11).…”

mentioning

confidence: 99%

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

Crouser¹,

Culver²,

Knox³

et al. 2009

Am J Respir Crit Care Med

135

126

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“…However, many of the other published instances are no better than the median of random tests (e.g. the Korkola et al [15] 'robust signature') or even worse than almost all (the Taube et al [16] 202-gene signature). It is also clear that sets comprising 100 or more genes are passable predictors of breast cancer survival, with p values in the range of 10 À4 -10 À5 , whatever the gene choice.…”

Section: Scanning Through Published Signaturesmentioning

confidence: 98%

Are expression profiles meaningless for cancer studies?

Jordan

2012

BioEssays

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Identification of a robust gene signature that predicts breast cancer outcome in independent data sets

Abstract: Background: Breast cancer is a heterogeneous disease, presenting with a wide range of histologic, clinical, and genetic features. Microarray technology has shown promise in predicting outcome in these patients.

Cited by 38 publications

References 32 publications

Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

Are expression profiles meaningless for cancer studies?

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