TS,ERCC1 MRNA Levels In Untreated Esophageal Cancer Tissue And Their Prediction To Efficacy Of Chemotherapy With Cisplatin And 5-fluorouracil

Esophageal carcinoma(EC) is one of the commonest cancers of the digestive tract, and surgery is the mainstay in the treatment of EC for a long time. However, because EC has a special anatomy location and a tendency to invade its adjacent tissue and organs, the postoperation survival rate has not been completely improved ,although the operative mortality declined greatly due to surgical procedure improvement. On the other hand, when EC patients are diagnosed, most of them are in the intermediate-advanced stage and the malignant cells have already disseminated,so that it is difficult to cure the patients by single surgery or radiotherapy or surgery plus radiotherapy. The main failure cause is the remote metastasis and local occurrence .At present, chemotherapy is the only effective approach to prevent and control systemic metastasis.Therefore, the chemotherapy plays an important role in EC comprehensive therapy, whether as a main modality for EC patients in advanced stage or as an adjuvant treatment for perioperative patients.Especially, the efficacy of multimodality therapy of EC has been further improved in recent years due to the preoperative chemotherapy. But chemotherapy is not always effective for all patients,therefore it is necessary to predict chemosensitivity of EC in order to make EC chemotherapy more directive,more effective and less blind.However,there has not been a better parameter untill now which may be used to assess the chemosensitivity.This research was designed to investigate the factors affecting the EC chemotherapy response at gene transcript level ,which may provide basis for individualized treatment of EC in clinic.Materials and methods:1. 20 endoscopic biopsy specimens of untreated EC were collected from the department of oncology of Hua county people hospital. These patients pathologically diagnosed are going to accept two cycles combined chemotherapy with cisplatin and 5-fluorouracil;cisplatin 80mg/m2was intravenously infused in consecutive three or five days and 5-fluorouracil 375 - 500 mg/m2/d was intravenously infused for eight hours per day in consecutive five days per cycle.The response to chemotherapy was evaluated by WHO efficacy evaluation criteria for solid tumours after chemotherapy.2. The mRNA levels of TS/p-actin and ERCCl/p-actin in EC tissue were determined by semi-quantitative reverse-transcription polymerase chain reaction(RT-PCR) and their correlations to the chemotherapy results were studied.3. Fisher's exact test was used to analyse the clinical pathology data between response and no response groups and to analyse the clinical pathology data and response differences between high and low TS and ERCC1 mRNA level groups. Differences of TS and ERCC1 mRNA level between response and no response groups was analysed by student's test .Spearman's correlation test was used to analyse the correlation between response and TS or/and ERCC1 mRNA levels.The prediction of TS and ERCC1 mRNA levels to response was analysed by forward and backward logistic regression analysis by SPSS 10.0 statistical program.There was a statistical significance when P (0.05 occurred with two-sided test.Results:1. The mean of TS and ERCC1 mRNA level of 20 untreated EC tissue was 7.39X10-1 and 9.56X10-1 respectively,the TS mRNA level range is from 2.84X10-1 to 1.27, and the highest level is approximately 4.5 times than that of the lowest; the range of ERCC1 mRNA level is from 3.7QX10-1 to 1.61, and the highest level is approximately 4.4 times than that of the lowest.2. The mean of ERCC1 mRNA level of 11 chemotherapy response EC patients was7.3xlO-1; and the mean of ERCC1 mRNA level of 9 no response EC patients was 1.1467. There was statistically significant difference between response and no response group (P<0.05) .3. The median of TS mRNA level of 11 chemotherapy response EC patients was3.9 10-1; and the median of TS mRNA level of 9 no response EC patients was9-1 10-1. There was statistically significant diff...