Preliminary Study Of Genes Related To The Concomitant Chemoradiotherapy Sensitivity In Locally Advanced Uterine Cervical Squamous Cell Carcinomas

Background and Objiects:Tumor intrinsic chemoradiotherapy sensitivity is one of the crutial reasons for concomitant chemoradiotherapy failure in advanced uterine cervical squamous cell carcinomas(UCSCC).This study aims to identify a set of genes and molecular function pathways related to the concomitant chemoradiotherapy sensitivity in UCSCC.Materials and methods:Forty cases of UCSCC patients in FIGO stageⅡb orⅢb treated with platinum based concomitant chemoradiotherapy in our hospital from October 2006 to October 2007 entered this trial.The chemoradiosensitive group and ehemoradioresistant group included 20 cases respectively.Tumor tissues were obtained by biopsy before treatment and total RNAs were extracted.22k Human Genome Oligonucleotide Microarrays carrying 21522 oligonucleotide probes were used to identify differentially expressed genes correlated with concomitant chemoradiotherapy sensitivity between the two groups(3 cases for each group).Molecular biology fuctional pathways analysis of differentially expressed genes was performed. Expression diffemtions of genes involved in several important pathways were further determined in next semiquantitative reverse transcription polymerase chain reactions (RT-PCR) in 40 cases.Results:Oligonucleotide Microarrays identified 108 significantly differentially expressed genes.Fifty-six genes were relatively higher expressed in resistant group and 52 relatively higher expressed in sensitive group.The fuctional pathways classes analysis of these genes demostrated many related pathways such as DNA damage repair, apoptosis,cell circle,Mapk signal transduction,anaerobic glycolysis and glutathione metabolism.We determined 14 genes involved in these pathways in RT-PCR.Seven of these 14 genes showed the same significant mRNA expression differention results with that in the microarray analysis:PDGFRAand PRKAR1Awere significantly higer expressed in chemoradiosensitive group(P＜0.05),while,LDHA,BAK1,BNIP3, SMUG1,CDK7were higer expressed in chemoradioresistant group(p＜0.05).The other 7 genes,CAST,IL1R1,RAN,TGFB3,GSTM3,HRAS and ATM showed no significant expression differention(p＞0.05) between the two group.The coincidence of predicted groups by combination of seven genes and clinical groups was 87.5%.Conclusions:Seven genes of PDGFRA,PRKAR1A,LDHA,BAK1,BNIP3,SMUG1 and CDK7 are related to the concomitant chemoradiotherapy sensitivity in UCSCC. Combination of these seven genes might be primary predictors for concomitant chemoradiotherapy sensitivity in UCSCC.