Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas.
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Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas. / Anders, Mario; Fehlker, Marion; Wang, Qing; Wissmann, Christoph; Pilarsky, Christian; Kemmner, Wolfgang; Höcker, Michael.
In: MOL CARCINOGEN, Vol. 52, No. 1, 1, 2013, p. 29-38.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas.
AU - Anders, Mario
AU - Fehlker, Marion
AU - Wang, Qing
AU - Wissmann, Christoph
AU - Pilarsky, Christian
AU - Kemmner, Wolfgang
AU - Höcker, Michael
N1 - Copyright © 2011 Wiley Periodicals, Inc.
PY - 2013
Y1 - 2013
N2 - Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray studies. Own microarray and quantitative RT-PCR data were obtained from a colorectal carcinoma cohort. Applying highly stringent inclusion criteria, 15 cancer array studies were suitable for our analysis. These studies provided 789 tumor specimens and 190 samples of healthy tissues yielding a total of approx. 1,000,000 gene expression measurements. Meta-analysis on the expression of 480 angiogenesis-related genes in 10 cancer types identified a characteristic, entity-independent "global" cancer expression signature of 25 angiogenesis-related genes showing high frequency down-regulation when compared to corresponding healthy tissues. Furthermore, we characterized 25 genes displaying frequent up-regulation, yet less often than the 25 down-regulated genes. Comparative inter-study cross-validation revealed that both signatures discriminate cancers from healthy tissues with high accuracy in independent test sets. Moreover, own microarray data of colorectal carcinomas confirmed the specific and sensitive discriminating potential of both signatures. These results were validated by quantitative RT-PCR for eight genes displaying the highest differences in the microarray analysis. Our study for the first time defines global gene expression signatures linked to angiogenesis in carcinomas. Our findings suggest that gene down-regulation may represent a central aspect of tumor angiogenesis.
AB - Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray studies. Own microarray and quantitative RT-PCR data were obtained from a colorectal carcinoma cohort. Applying highly stringent inclusion criteria, 15 cancer array studies were suitable for our analysis. These studies provided 789 tumor specimens and 190 samples of healthy tissues yielding a total of approx. 1,000,000 gene expression measurements. Meta-analysis on the expression of 480 angiogenesis-related genes in 10 cancer types identified a characteristic, entity-independent "global" cancer expression signature of 25 angiogenesis-related genes showing high frequency down-regulation when compared to corresponding healthy tissues. Furthermore, we characterized 25 genes displaying frequent up-regulation, yet less often than the 25 down-regulated genes. Comparative inter-study cross-validation revealed that both signatures discriminate cancers from healthy tissues with high accuracy in independent test sets. Moreover, own microarray data of colorectal carcinomas confirmed the specific and sensitive discriminating potential of both signatures. These results were validated by quantitative RT-PCR for eight genes displaying the highest differences in the microarray analysis. Our study for the first time defines global gene expression signatures linked to angiogenesis in carcinomas. Our findings suggest that gene down-regulation may represent a central aspect of tumor angiogenesis.
KW - Carcinoma
KW - Colorectal Neoplasms
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Male
KW - Neovascularization, Pathologic
KW - Oligonucleotide Array Sequence Analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Transcriptome
U2 - 10.1002/mc.20874
DO - 10.1002/mc.20874
M3 - SCORING: Journal article
C2 - 22012870
VL - 52
SP - 29
EP - 38
JO - MOL CARCINOGEN
JF - MOL CARCINOGEN
SN - 0899-1987
IS - 1
M1 - 1
ER -
