TS MRNA And BRCA1mRNA As Predictive Biomarkers In Individualized Treatment In Colorectal Cancer

Part I Thymidylate synthase(TS) mRNA expression levels as potential predictive biomarkers for raltitrexed sensitivity in colorectal cancerBackground:With the rapid development in individual treatment since 2004, more and more biomarkers have been screened and validated. Tailor chemotherapy based on the specific genetic profile of individual patients has come of age. In an attempt to improve the clinical efficiency, it is important and necessary to identify biomarkers capable of discriminating the patients who are likely to respond to certain chemotherapeutic agents. The aim of this study was to investigate the role of TS mRNA in tumor tissue as a predictive biomarker for raltitrexed in colorectal cancer.Methods:50 freshly-removed colorectal tumor specimens before surgery were collected. Histoculture drug response assay(HDRA) was adopted to assess raltitrexed and pemetrexed and 5-FU sensitivity. TS mRNA was determined by RT-PCR. TS protein expression was evaluated by immunohistochemical staining.Results:TS mRNA levels were lower in pemetrexed-sensitive group/raltitrexed-sensitive group/5-FU-sensitive group than resistant groups in our study (pemetrexed:P< 0.001; raltitrexed:P= 0.004; 5-FU:P= 0.007). There was no relationship between TS protein expression and TS mRNA levels(P=0.16).Conclusion:These results indicate that TS mRNA levels can predict pemetrexed/raltitrexed/5-FU sensitivity in colorectal caner.Part II BRCA1 mRNA expression levels as poteMiai predictive biomarkers for docetaxel and oxaliplatin sensitivity in colorectal cancerBackground:Personalized chemotherapy based on predictive biomarkers can improve the clinical efficiency. Oxaliplatin was used for colorectal cancer for several years. Moreover, BRCA1mRNAhas been reported as potential predictive biomarker in lung cancer and other cancers.Methods:we collected Freshly-removed colorectal tumor specimens from 50 patients. Chemosensitivities to docetaxel and oxaliplatin were determined by histoculture drug response assay (HDRA); we adopted quantitative RT-PCR (qRT-PCR) for BRCA1 mRNA detection.Results:There was no significant association between clinical characteristics and in vitro chemosensitivity or BRCA1 mRNA levels. BRCA1 mRNA levels in oxaliplatin-sensitive group were significanly lower than resistant groups(P<0.05).Conclusion:BRCA1 mRNA expression level in colorectal cancer was negatively correlated with in vitro chemo sensitivity to oxaliplatin in colorectal cancer. There was no relationship between BRCA1mRNA expression and in vitro chemosensitivity to docetaxel in colorectal cancer.