The Research Of The Relationship Between Efficacy-related Gene Expression Levels And Drug Sensitivities In Esophageal Cancer

Objective:To explore the relationship between gene expression level and drug sensitivity in fresh tumor tissues of esophageal cancer.Methods:1.Histoculture Drug Response Assay(HDRA)was employed to detect the drug-sensitivity of fresh tumor tissues to cisplatin,docetaxel,5-FU,irinotecan,etoposide,gemcitabine and gefitinib.2.Expression levels of efficacy-related genes(ERCC1,BRCA1,β-Tubulin III,FBW7,TS,TOP1 MDM2 and RRM1)was evaluated by quantitative reverse transcription polymerase chain reaction(qPCR).3.The relationship between expression levels of efficacy-related genes and drug-sensitivity was analysed with SPSS 19.0.Results:1.Results of HDRA showed:● the drug-sensitivity of gefitinib to tumor tissues was low with inhibition rate.Response rate of gefitinib in 300uM was only 13.0%(3/23)if inhibition rate more than 30%was considered as sensitive.● the work concentration of drugs were confirmed with inhibition rate of more than 30%in preliminary experiment(cisplatin:100ug/ml,docetaxel:30ug/ml,5-Fu:10ug/ml,irinotecan:100ug/ml etoposide:100ug/ml and gemcitabine:30ug/ml).● the high sensitivity of cisplatin was correlated with the low TNM stage in esophageal cancer(P=0.006).Furtherly,the correlation between clinicopathology characteristics and other drug-sensitivity(docetaxel,5-Fu,etoposide,irinotecan,gemcitabine and gefitinib)were not observed in our study(all P>0.05).2.Genes expression in fresh tissues of esophageal cancer by qPCR:● the positive correlation was reached between ERCC1 and BRCA1 mRNA expression(Pearson’s test 0.367;P= 0.009).● the positive correlation was reached between BRCA1 and 0-Tubulin III mRNA expression(Pearson’s test 0.356;P= 0.012).● TS mRNA expression levels was correlated to the age of patients(P=0.024),whereas no correlation was observed between the other genes expression and clinicopathology characteristics in esophageal cancer(all P>0.05).3.The relationship between genes expression levels and drug-sensitivities showed that low expression of BRCA1,TS and TOP1 mRNA was correlated with the high drug-sensitivity for cisplatin(P=0.032),5-Fu(P=0.032)and irinotecan(P= 0.007),respectively.Conclusions:1.The fresh tissue of esophageal cancer was not sensitive to gefitinib in our research.2.Results of HDRA showed that BRCA1,TS,TOP1 mRNA expression levels were correlated with cisplatin,5-Fu and irinotecan respectively which reminded that BRCA1,TS,TOP1 mRNA expression levels could be used as predictive factors for cisplatin,5-Fu and irinotecan in esophageal cancer respectively.