The Correlation Study Between The Polymorphism Of ERCC1Gene C19007T And The Expression Of MRP, GST-Ï€, P-gp And LRP In Human Colorectal Carcinoma

Objective:Colorectal carcinoma is one of high incidence of malignant tumor ofdigestive system in our country. In last few years the incidence and mortalityof colorectal carcinoma have an increased trend, the age of onset is becomingyounger and younger. Surgical operation combined with chemotherapy is themain measure of clinical treatment of colorectal carcinoma, and especially topatients with advanced colorectal carcinoma those who have missed thechance of operation, chemotherapy may be the only treatment. Chemotherapycan effectively inhibit colorectal carcinoma recurrence and prevent themetastasis, so the success or failure of the chemotherapy will affect directlythe prognosis of patients. In recent years, studies have shown that MRP, GST-π, P-gp and LRP can induce multi-drug resistance of tumor cells, change thesensitivity of tumor cells to chemotherapy drugs, thus affecting the curativeeffect of chemotherapy. At the same time, the ERCC1gene polymorphism isclosely related to platinum drugs resistant, prediction of the efficacy ofchemotherapy and prognosis judgment. We try to do some experiments todetermine the expression of MRP, GST-π, P-gp and LRP in differentgenotypes of ERCC1C19007T in patients with colorectal carcinoma, toelucidate the relationship between ERCC1gene C19007T polymorphism andmultiple drug resistance protein in colorectal carcinoma, provide referenceindex for determining clinically chemotherapy sensitivity in differentgenotypes of ERCC1gene C19007T of patients with colorectal cacinoma, andprovide theoretical foundation for reasonable individual chemotherapyregimen. Methods:We randomly selected the86cases of specimen of patients withcolorectal carcinoma and52cases of distal normal tissue from cancer (>10cm).The S-P immunohistochemical method was used to examine the expression ofMRP, GST-π, P-gp and LRP in86cases of colorectal carcinoma tissues and52cases of distal normal tissues from cancer (>10cm). The correlationsbetween the expression and the clinicopathological features (such as sex、age、tumor size、tumor location、histological types、lymph node metastasis) of thecancer were analyzed. At the same time, we took all the86cases of specimenof patients with colorectal carcinoma and stored them at-80℃, DNA wasextracted from tissues of colorectal carcinoma by TIANamp Genomic DNAkit. ERCC1gene C19007T polymorphism in86cases of colorectal carcinomawere examined by polymerase chain reaction-restriction fragment lengthpolymorphism(PCR-RFLP). And the correlations between the expression anddifferent genotypes of ERCC1C19007T were analyzed.Results:The result of PCR-RFLP showed that genotype frequencies of ERCC1C19007T were C/C53.49%（46/86）, C/T40.70%（35/86）, and T/T5.81%（5/86）. The result of immunochemical showed that the positive expressionrate of MRP in86cases of tissues of colorectal carcinoma was45.3%, that ofGST-π was72.09%(62/86), that of P-gp was79.07%, and that of LRP was76.7%, the expression in tissues of colorectal carcinoma were higher than thatin the distal normal tissues (P<0.05). The expression of MRP was closelycorrelated with the differentiation of colorectal carcinoma, the positiveexpression rate in lowly differentiated group (61.0%) was higher than that inhighly and moderately differentiated group (31.1%), and the difference wassignificant (P<0.01). The expression of P-gp is closely correlated with lymphnode metastasis, the positive expression rate in group with lymph nodemetastasis (87.76%) is higher than that in group without lymph nodemetastasis (67.57%), and the difference was significant (P<0.05). Among thetotal, the positive expression rate of GST-πin C/T plus T/T genotype groups(85.00%) is higher than that in C/C genotype groups (60.87%), and the difference was significant（P<0.05）. The positive expression rate of LRP inC/T plus T/T genotype groups (90.00%)is higher than that in C/C genotypegroups (65.22%), and the difference was significant（P<0.05）. There was nosignificant difference in expression of MRP between the two groups. Andthere was no significant difference in expression of P-gp between the twogroups.Conclusions:(1) MRP, GST-π, P-gp and LRP were over expressed in various degreesin colorectal cancer, and may be associated with the multidrug resistance ofthe colorectal cacinoma.(2)The expression of MRP in colorectal carcinoma had no relations withsex, age, tumor size, tumor location and lymph node metastasis （P>0.05）.But that of MRP related to differentiation: the positive expression rate in lowlydifferentiated group was higher than that in highly and moderatelydifferentiated group.(3)The expression of P-gp in colorectal carcinoma had no relations withsex, age, tumor size, tumor location and differentiation degree(P＞0.05). Butthe expression of P-gp was closely correlated with lymph node metastasis, thepositive expression rate in group with lymph node metastasis was higher thanthat in group without lymph node metastasis.(4)ERCC1gene polymorphism was associated with sensitivity forchemotherapeutic drugs to colorectal carcinoma, the detection of ERCC1C19007T genotype may help to guide the chemotherapy of colorectalcarcinoma.