Identification of genes associated with progression and metastasis of advanced cervical cancers after radiotherapy by cDNA microarray analysis.
OBJECTIVE
To identify a set of genes related to the progression and metastasis of advanced cervical cancer after radiotherapy and to establish a predictive method.


METHODS
A total of 28 patients with cervical cancer (15 stage IIIB, 13 stage IVA patients) who underwent definitive radiotherapy between May 1995 and April 2001 were included in this study. All patients were positive for human papillomavirus infection and harbored the wild-type p53 gene. The expression profiles of 14 tumors with local failure and multiple distant metastasis and 14 tumors without metastasis (cancer free) obtained by punch biopsy were compared before treatment, using a cDNA microarray consisting of 23,040 human genes.


RESULTS
Sixty-three genes were selected on the basis of a clustering analysis, and the validity of these genes was confirmed using a cross-validation test. The most accurate prediction was achieved for 63 genes (sensitivity, 78.8%; specificity, 38.1%). Some of these genes were already known to be associated with metastasis via chromosomal instability (TTK, BUB1B), extracellular matrix components (matrix metalloproteinase 1 [MMP-1]), and carcinogenesis (protein phosphatase 1 regulatory subunit 7 [PPP1R7]). A "predictive score" system was developed that could predict the probability for development of metastases using leave-one-out cross-validation methods.


CONCLUSIONS
The present results may provide valuable information for identified predictive markers and novel therapeutic target molecules for progression and metastasis of advanced cervical cancer.
Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka, Japan. harima@takii.kmu.ac.jp
Yoko
Y
Harima
Koshi
K
Ikeda
Keita
K
Utsunomiya
Toshiko
T
Shiga
Atsushi
A
Komemushi
Hiroyuki
H
Kojima
Motoo
M
Nomura
Minoru
M
Kamata
Satoshi
S
Sawada
D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy
D005819:Genetic Markers