Identification of expressed genes linked to malignancy of human colorectal carcinoma by parametric clustering of quantitative expression data.
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.
Muro
Shizuko
S
Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
Takemasa
Ichiro
I
Oba
Shigeyuki
S
Matoba
Ryo
R
Ueno
Noriko
N
Maruyama
Chiyuri
C
Yamashita
Riu
R
Sekimoto
Mitsugu
M
Yamamoto
Hirofumi
H
Nakamori
Shoji
S
Monden
Morito
M
Ishii
Shin
S
Kato
Kikuya
K
D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007564:Japan; D025202:Molecular Diagnostic Techniques; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D015996:Survival Rate