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Identification of expressed genes linked to malignancy of human colorectal carcinoma by parametric clustering of quantitative expression data.

Muro S, Takemasa I, Oba S, Matoba R, Ueno N, Maruyama C, Yamashita R, Sekimoto M, Yamamoto H, Nakamori S, Monden M, Ishii S, Kato K - Genome Biol. (2003)

Bottom Line: Approximately half showed an identical expression pattern, and cancer tissues were classified into two groups by their expression levels.The high-expression group had strong correlation with distant metastasis, and a poorer survival rate than the low-expression group, indicating possible clinical applications of these genes.In addition to c-yes, a homolog of a viral oncogene, prognostic indicators included genes specific to glial cells, which gives a new link between malignancy and ectopic gene expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.

ABSTRACT

Background: Individual human carcinomas have distinct biological and clinical properties: gene-expression profiling is expected to unveil the underlying molecular features. Particular interest has been focused on potential diagnostic and therapeutic applications. Solid tumors, such as colorectal carcinoma, present additional obstacles for experimental and data analysis.

Results: We analyzed the expression levels of 1,536 genes in 100 colorectal cancer and 11 normal tissues using adaptor-tagged competitive PCR, a high-throughput reverse transcription-PCR technique. A parametric clustering method using the Gaussian mixture model and the Bayes inference revealed three groups of expressed genes. Two contained large numbers of genes. One of these groups correlated well with both the differences between tumor and normal tissues and the presence or absence of distant metastasis, whereas the other correlated only with the tumor/normal difference. The third group comprised a small number of genes. Approximately half showed an identical expression pattern, and cancer tissues were classified into two groups by their expression levels. The high-expression group had strong correlation with distant metastasis, and a poorer survival rate than the low-expression group, indicating possible clinical applications of these genes. In addition to c-yes, a homolog of a viral oncogene, prognostic indicators included genes specific to glial cells, which gives a new link between malignancy and ectopic gene expression.

Conclusions: The malignancy of human colorectal carcinoma is correlated with a unique expression pattern of a specific group of genes, allowing the classification of tumor tissues into two clinically distinct groups.

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Correlation of gene expression with cancer phenotype. The vertical axis represents the correlation ratio (CR) of the differences between tumor and normal tissues in (a) group GM-A and (b) GM-B; or the presence or absence of distant metastasis in (c) GM-A and (d) GM-B; or lymph node metastasis in (e) GM-A and (f) GM-B. The horizontal axis represents the genes sorted by CR. Red, original data; blue, trials of permuted data.
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Figure 5: Correlation of gene expression with cancer phenotype. The vertical axis represents the correlation ratio (CR) of the differences between tumor and normal tissues in (a) group GM-A and (b) GM-B; or the presence or absence of distant metastasis in (c) GM-A and (d) GM-B; or lymph node metastasis in (e) GM-A and (f) GM-B. The horizontal axis represents the genes sorted by CR. Red, original data; blue, trials of permuted data.

Mentions: Genes selected by supervised methods, such as selection based on correlation with a clinical parameter, include those universally correlated with the parameter and those correlating only within the analyzed sample set. To avoid the uncertainty inherent in supervised methods, we examined the correlations between clinical phenotypes and gene groups instead of individual genes. We devised a correlation ratio (CR) to serve as an indicator for correlation with clinical parameters. Genes were first sorted by CR value order, and then the CRs of the original total dataset were compared with those of permuted data (Figure 5). In group GM-A, the CRs were significantly higher than those of the total dataset for both the differences between tumor and normal tissues and the presence or absence of distant metastases (Figure 5a,c). In contrast, the GM-B group possessed a high CR only for the difference between tumor and normal tissues (Figure 5b,b). For these parameters, the CR values of the total dataset were consistently higher throughout the full range of CRs, suggesting the correlation was not restricted to a small number of genes, but was a global character of each group (Figure 5a,b,c). We could not identify significant correlations for other parameters, including lymph-node metastases (Figure 5e,f) and histological type (data not shown).


Identification of expressed genes linked to malignancy of human colorectal carcinoma by parametric clustering of quantitative expression data.

Muro S, Takemasa I, Oba S, Matoba R, Ueno N, Maruyama C, Yamashita R, Sekimoto M, Yamamoto H, Nakamori S, Monden M, Ishii S, Kato K - Genome Biol. (2003)

Correlation of gene expression with cancer phenotype. The vertical axis represents the correlation ratio (CR) of the differences between tumor and normal tissues in (a) group GM-A and (b) GM-B; or the presence or absence of distant metastasis in (c) GM-A and (d) GM-B; or lymph node metastasis in (e) GM-A and (f) GM-B. The horizontal axis represents the genes sorted by CR. Red, original data; blue, trials of permuted data.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC153461&req=5

Figure 5: Correlation of gene expression with cancer phenotype. The vertical axis represents the correlation ratio (CR) of the differences between tumor and normal tissues in (a) group GM-A and (b) GM-B; or the presence or absence of distant metastasis in (c) GM-A and (d) GM-B; or lymph node metastasis in (e) GM-A and (f) GM-B. The horizontal axis represents the genes sorted by CR. Red, original data; blue, trials of permuted data.
Mentions: Genes selected by supervised methods, such as selection based on correlation with a clinical parameter, include those universally correlated with the parameter and those correlating only within the analyzed sample set. To avoid the uncertainty inherent in supervised methods, we examined the correlations between clinical phenotypes and gene groups instead of individual genes. We devised a correlation ratio (CR) to serve as an indicator for correlation with clinical parameters. Genes were first sorted by CR value order, and then the CRs of the original total dataset were compared with those of permuted data (Figure 5). In group GM-A, the CRs were significantly higher than those of the total dataset for both the differences between tumor and normal tissues and the presence or absence of distant metastases (Figure 5a,c). In contrast, the GM-B group possessed a high CR only for the difference between tumor and normal tissues (Figure 5b,b). For these parameters, the CR values of the total dataset were consistently higher throughout the full range of CRs, suggesting the correlation was not restricted to a small number of genes, but was a global character of each group (Figure 5a,b,c). We could not identify significant correlations for other parameters, including lymph-node metastases (Figure 5e,f) and histological type (data not shown).

Bottom Line: Approximately half showed an identical expression pattern, and cancer tissues were classified into two groups by their expression levels.The high-expression group had strong correlation with distant metastasis, and a poorer survival rate than the low-expression group, indicating possible clinical applications of these genes.In addition to c-yes, a homolog of a viral oncogene, prognostic indicators included genes specific to glial cells, which gives a new link between malignancy and ectopic gene expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.

ABSTRACT

Background: Individual human carcinomas have distinct biological and clinical properties: gene-expression profiling is expected to unveil the underlying molecular features. Particular interest has been focused on potential diagnostic and therapeutic applications. Solid tumors, such as colorectal carcinoma, present additional obstacles for experimental and data analysis.

Results: We analyzed the expression levels of 1,536 genes in 100 colorectal cancer and 11 normal tissues using adaptor-tagged competitive PCR, a high-throughput reverse transcription-PCR technique. A parametric clustering method using the Gaussian mixture model and the Bayes inference revealed three groups of expressed genes. Two contained large numbers of genes. One of these groups correlated well with both the differences between tumor and normal tissues and the presence or absence of distant metastasis, whereas the other correlated only with the tumor/normal difference. The third group comprised a small number of genes. Approximately half showed an identical expression pattern, and cancer tissues were classified into two groups by their expression levels. The high-expression group had strong correlation with distant metastasis, and a poorer survival rate than the low-expression group, indicating possible clinical applications of these genes. In addition to c-yes, a homolog of a viral oncogene, prognostic indicators included genes specific to glial cells, which gives a new link between malignancy and ectopic gene expression.

Conclusions: The malignancy of human colorectal carcinoma is correlated with a unique expression pattern of a specific group of genes, allowing the classification of tumor tissues into two clinically distinct groups.

Show MeSH
Related in: MedlinePlus