Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study.
OBJECTIVE
To determine the feasibility of integrating an in vitro chemo-radiation response assay (IVRRA) with a gene microarray system to investigate the molecular patterns of expression that contribute to radiation resistance in cervical cancer.


METHODS
Viable primary untreated cervical cancer specimens were obtained and exposed to gamma irradiation at a dose of 3 Gy in the IVRRA to determine in vitro radiation sensitivity. RNA was purified for microarray analysis with the Affymetrix Human Genome U95A Array carrying more than 12,000 gene probes. Gene expression analysis was performed, and specimen transcript patterns were correlated with radiation response using an iteration analysis model and Pearson's correlation coefficient.


RESULTS
A feasibility set of eight tumor specimens was studied. Tumors were classified into 4 extreme (ERR), 2 intermediate (IRR) and 2 low radiation resistance (LRR) categories. An intrinsic radiation response gene set of 54 genes transcripts with 100% accuracy for the classification of each tumor's radiation response category was identified.


CONCLUSIONS
Gene sets associated with in vitro radiation response profiles in cervical cancer can be generated using the IVRRA and microarray technology. This has direct applications to the study of the biological pathways contributing to radiation resistance and may lead to the development of alternative treatment modalities. The potential of these technologies for cancers in which radiotherapy is employed warrants further investigation.
Tewari
Devansu
D
Division of Gynecologic Oncology, University of California Irvine Medical Center, 101 The City Drive South, Orange, CA 92868, USA.
Monk
Bradley J
BJ
Al-Ghazi
Muthana S
MS
Parker
Ricardo
R
Heck
J Denis
JD
Burger
Robert A
RA
Fruehauf
John P
JP
D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011836:Radiation Tolerance / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D012334:RNA, Neoplasm