[Molecular classification of colorectal carcinoma based on integration of gene expression profile and copy number variation].
Zhejiang Da Xue Xue Bao Yi Xue Ban
; 43(4): 420-6, 2014 07.
Article
en Zh
| MEDLINE
| ID: mdl-25187456
OBJECTIVE: To classify colorectal carcinoma (CRC) by TNM staging integrated with the gene expression profile and copy number variation (CNV). METHODS: Profile data of gene expression and CNV of CRC were downloaded from public database and processed with batch bias adjustment, quartile normalization, missing value estimation and feature filtration. The processed profiles of mRNA and CNV were introduced into the codes of Bayesian consensus clustering (BCC) method and were used to calculate the subclasses of CRC. With the follow-up information of disease free survival of CRC patients, the prognostic values of the subclasses was investigated and the software of function enrichment analysis was employed to discover the major pathway signaling to each interesting subclass. All statistic analyses were performed under R-3.0.1 environment or by using SPSS 16.0 software. RESULTS: Profile data of gene expression and corresponding CNV from 335 CRC patients with TNM stage â
¡-â
¢ and followed-up information were obtained. After feature filtering, the profiles contained 1578 probes of mRNA and 345 location of CNV. Four CRC subclasses were identified by the integrative analysis with BCC, and the concordances of BCC subclasses and each of gene-based subclasses (Cramer's V=0.49), CNV-based subclasses (Cramer's V=0.51) and Marisa's subclasses (Cramer's V=0.32) were statistically significant (Ps<0.001). Among BCC subclasses, BCC-I had a favorable prognosis, while BCC-â
£ had more unfavorable prognosis. The differences of prognosis were significant among BCC-I, BCC-(â
¡+â
¢) and BCC-â
£ with an overall log-rank P<0.001. The top enriched function was DNA damage and repair signaling when BCC-I compared to BCC-â
£, and the new subgroups classified by the genes associated with enriched signaling had the better prognostic value than BCC subclasses but both of them were significantly correlated (Cramer's V=0.39, P<0.001). CONCLUSION: BCC method is effective to integrate multi-type genomic data for molecular classification of colorectal carcinoma, and the BCC-â
£ subclass has poor prognosis, which may be associated with the decreased repairing function of DNA damage.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Variaciones en el Número de Copia de ADN
/
Transcriptoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
Zh
Revista:
Zhejiang Da Xue Xue Bao Yi Xue Ban
Asunto de la revista:
MEDICINA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
China