Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis.
OBJECTIVE
To identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method.


METHODS
A total of 19 patients with cervical cancer (1 with Stage IIIA, 11 with Stage IIIB, 5 with Stage IVA, and 2 with Stage IVB) who underwent definitive thermoradiotherapy between May 1995 and August 2001 were included in this study. We compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes.


RESULTS
We selected 35 genes on the basis of a clustering analysis and confirmed the validity of these genes with a cross-validation test. Some of these genes were already known to be associated with apoptosis (BIK, TEGT, SSI-3), hypoxia-inducible genes (HIF1A, CA12), and tumor cell invasion and metastasis (CTSL, CTSB, PLAU, CD44). We developed a "predictive score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant group.


CONCLUSIONS
These results from the treatment program between May 1995 and August 2001 showed that by using gene-expression profiles we can predict the outcome of thermoradiotherapy for advanced cervical carcinoma. A "predictive score" system was developed that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. These results may eventually lead to the achievement of "personalized therapy" for this disease.
Harima
Yoko
Y
Department of Radiology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8507, Japan. harima@takii.kmu.ac.jp
Togashi
Akira
A
Horikoshi
Kenichi
K
Imamura
Masahiro
M
Sougawa
Mitsuharu
M
Sawada
Satoshi
S
Tsunoda
Tatsuhiko
T
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*