Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

BMC Cancer

Michael Pierre²  Benoît DeHertogh²  Anthoula Gaigneaux²  Bertrand DeMeulder²  Fabrice Berger²  Eric Bareke²  Carine Michiels¹  Eric Depiereux² 

[1] Cell Biology Research Unit (URBC), University of Namur - FUNDP, Namur, Belgium

[2] Molecular Biology Research Unit (URBM), University of Namur - FUNDP, Namur, Belgium

Others  :  1081654
DOI  :  10.1186/1471-2407-10-176

 received in 2009-07-30, accepted in 2010-04-30,  发布年份 2010

【 摘 要 】

Background

Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines.

Methods

Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest.

Results

Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known JUNB, FOS and TP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as SERPINE1 and MMP7, are known to regulate metastasis. Twenty-one genes including VEGFA and ID2 have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis.

Conclusion

The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in the metastatic phenotype induced by hypoxia.

【 授权许可】

   
2010 Pierre et al; licensee BioMed Central Ltd.

【 图 表 】

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