Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Comparative profiling of primary colorectal carcinomas and liver metastases

ABSTRACT: PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) of the expressed genes between these two groups. To characterize the clinical relevance of two highly-ranked differentially expressed signature genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.035), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p < 0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p < 0.0001) and LEF1 overexpression (p < 0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among signature genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 31 freshly-frozen primary colorectal cancer specimens, and compared to published profiles of 32 unmatched colorectal liver metastases and 12 normal liver specimens.

ORGANISM(S): Homo sapiens

SUBMITTER: Jonathan Pollack

PROVIDER: E-GEOD-22834 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker.

Lin Albert Y AY Chua Mei-Sze MS Choi Yoon-La YL Yeh William W Kim Young H YH Azzi Raymond R Adams Gregg A GA Sainani Kristin K van de Rijn Matt M So Samuel K SK Pollack Jonathan R JR

PloS one 20110224 2

<h4>Purpose</h4>We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC).<h4>Patients and methods</h4>We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of tw ...[more]

PMID: 21383983

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Comparative profiling of primary colorectal carcinomas and liver metastases

Publications

Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker.

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