| Gastroenteric tumor is one of the most common malignancies in the world. In China, the morbidity and mortality of gastroenteric tumor are very high in all malignant tumors. At present, chemotherapy is an important means of treatment for the cancer patients. But the efficacy is different in the patients with same chemotherapy regimen, and also in prognosis. This shows that the sensitivity to chemotherapy in each patient is different. One of the important reasons which caurse differences in chemotherapy sensitivity is genetic variation, which can influence the protein expression and biological activity. This genetic variation can adjust the antitumor drug metabolism and its function, and then affect the individual reaction of chemotherapy. Recent advances in tumor resistance of chemotherapy have revealed that seeking to measure tumor markers of chemotherapeutic drug sensitivity has gradually became the research focal point. The tumor chemosensitive genes of thymidylate synthase gene (TYMS) and excision repair cross-complementing gene1(ERCC1) were earliest concerned. The majority reports confirmed that the28bps tandem repeat of polymorphism in TYMS gene5’-untranslated region enhancer region can influence the stability of TYMS mRNA and the expression. According to the number of this sequence repeats, the genotype of TYMS can be mainly divided into two types which are two repeats (2R) and three repeats (3R), so the most common genotypes are3R/3R、2R/2R and2R/3R. This polymorphism in TYMS has been revealed to be associated with variations in the expression leves of TYMS. The product of TYMS gene is one of the important targets of5-Fu. Therefore, the therapeutic efficacy of5-Fu therapy is correlated with the polymorphism of TYSM. The expression of ERCCl gene is the lead enzyme in the nucleotide excision repair process. High ERCCl levels are associated with increased removal of platinum-induced DNA adducts and relative platinum resistance. The mutation in codon118of the fourth exon of ERCC1in T/C base can reduce the expression level of ERCC1protein, which can reduce the DNA repair capacity of ERCC1.Clinically, lower expression of ERCC1level can assiociated with improved tumor response and efficacy of platinum.At present, the majority detections of chemosensitive gene in clinical are using cancer tissues. Because of individual differences in patients, not suitable for operation or other reasons, cancer tissues are difficult to access. In addition, many factors can influence the extraction process of tissue nucleic acid. Therefore, to seek a convenient and accessible specimen type for detection of polymorphism of tumor chemotherapy sensitivity related gene is urgent, which will have important theoretical and pactical significance for the patients with individual cancer treatment plan.In rencent years, it was reported that the polymorphisms of TYMS and ERCC1can be detected in blood of patients with digestive tract tumor. But, it is unclear whether the polymorphism of TYMS and ERCC1gene could be detected in peripheral blood of patients with gastric cancer and whether these polymorphisms are accordance in tumor tissues and peripheral blood. Through the detection of TYMS and ERCCl gene polymorphism in gastric cancer tissues and peripheral blood, we researched whether the polymorphism of TYMS and ERCCl gene in tumor tissue and in peripheral blood was consistent and whether blood gene polymorphism detection instead of tissues. On this basis, we collected peripheral blood of digestive tract tumor patients who based on5-Fu and platinum-based chemotherapy. To study the evaluation of tumor chemotherapy sensitivity gene TYMS and ERCCl on the effect of chemotherapy in peripheral venous blood of patients with gastroenteric tumor will provide a simple laboratory evaluation measure for tumor patients with individual treatment.Methods1. Experimental groups:(1) Specimens of patients with non-chemotherapy groups: The peripheral venous blood and tumor tissue samples of43GC patients were collected, and divided into peripheral blood group and tumor tissue group.(2) Specimens of patients with chemotherapy groups:The peripheral venous blood of76patients with5-Fu and platinum-based chemotherapy of cancer patients were collected.Evaluate the efficacy of chemotherapy for patients with evaluation standard of curative effect in solid tumors (RECIST), and divided into effective chemotherapy group including the cases of complete remission (CR) and partial remission (PR) and ineffective group including the cases of stable disease (SD) and the progression of disease(PD).2. The genotypes of TYMS、ERCC1were detected by PCR and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).3. SPSS17.0statistical software was applied for the data statistics. The experiment data was expressed with the number of samples. Spearman was used for analysising the correlation between sample groups. The two groups were compared with Chi-square continuity correction.Fisher test was used for analysis of the relationship between the genotypes and the efficacy of chemotherapy.The test results of P<0.05for difference was statistically significant.Results1. There was no significant correlation between the genotypes of TYMS and ERCC1and the clinical pathological factors of GC patients (P>0.05).2. In peripheral blood and tumor tissue, the detection rates of the3R/3R,(2R/2R,2R/3R) genotype of TYMS were72.09%(31/43),27.91%(12/46); and the detection rates of the C/C,(T/T, C/T) genotype of ERCC1were81.39%(35/43),18.61%(8/43).The detection rates of genotypes of TYMS and ERCC1 were consistent (P<0.01).3. According to the RECIST standard, the results of the evaluation of short term efficacy of chemotherapy patients was CR0cases, PR24cases,SD18cases and PD34cases.4. The detection rates of3R/3R,(2R/2R,2R/3R) genotype of TYMS gene in chemotherapy patients were65.79%(50/76),34.21%(26/76). Patients carrying the3R/3R genotype were50cases. Effective chemotherapy group were9cases including CR0case, PR9casess, and ineffective chemotherapy group were41cases including SD14cases and PD27case. The effective rate of chemotherapy was18%(9/50). Patients carrying the2R/2R and2R/3R genotypes were26cases. Effective chemotherapy group were15cases including CR0case, PR15casess, and ineffective chemotherapy group were11cases including SD4cases and PD7cases. The effective rate of chemotherapy was57.69%(15/26). There was a significant correlation through statistical analysis (P<0.05).5. The detection rates of C/C,(T/T, C/T) genotype of ERCC1gene in chemotherapy patients were63.16%(48/76),36.84%(26/76). Patients carrying the C/C genotype were48cases. Effective chemotherapy group were23cases including CR0case, PR23casess, and ineffective chemotherapy group were25cases including SD10cases and PD15case. The effective rate of chemotherapy was47.,91%(23/48). Patients carrying the T/T and C/T genotypes were28cases. Effective chemotherapy group were1cases including CR0case, PR1casess, and ineffective chemotherapy group were27cases including SD8cases and PD19case. The effective rate of chemotherapy was3.57%(1/28). There was a significant correlation through statistical analysis (P<0.05).Conclusions1. The peripheral venous blood samples can replace tumor tissue samples to detect the polymorphism of TYMS and ERCC1gene.2. In the chemotherapy of5-Fu, the efficacy in patients carrying2R/2R or2R/3R genotype of TYMS gene is good, and in the patients carrying3R/3R genotype is poor. It is suggested that the polymorphism of tumor chemosensitive gene TYMS can be used to evaluate the efficacy of5-Fu in peripheral venous blood.3. In the chemotherapy of platinum drugs, the efficacy in patients carrying C/C genotype of ERCC1gene is good, and in the patients carrying T/T or T/C genotype is poor. It is suggested that the polymorphism of tumor chemosensitive gene ERCCl can be used to evaluate the efficacy of platinum drugs in peripheral venous blood. |
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