Study On The Relationship Between ABCB1 Gene Polymorphism And Toxicity And Short-term Efficacy Of First-line Chemotherapy For Ovarian Cancer

Objective1.To investigate the basic situation of SNP in patients with ovarian cancer,and to study the expression level of ABCB1 in normal tissues and ovarian cancer tissues and its relationship with clinical data and prognosis of patients with ovarian cancer.2.To explore the relationship between ABCB1 gene polymorphism and side effects and short-term efficacy of platinum regimen chemotherapy in patients with ovarian cancer.MethodsBased on TCGA and GTEx database,the SNP data and RNA-seq data of patients with ovarian cancer were analyzed by bioinformatics.Forty patients with ovarian cancer were selected from the 940 th Hospital of the Joint Logistics support Force of the Chinese people's Liberation Army and the Maternal and Child Health Hospital of Gansu Province from October 2017 to June 2019.Forty patients with ovarian cancer were treated with platinum combined with paclitaxel for 6 courses.G2677T/An and C3435 T genotypes of ABCB1 in samples were detected by in situ hybridization.2-test and Logistic regression were used to analyze the relationship between ABCB1 gene polymorphism and toxicity and short-term efficacy of first-line chemotherapy in patients with ovarian cancer.Results1.Based on TCGA database,the top 15 genes with high incidence of gene mutation in patients with ovarian cancer were TP53,TTN,MUC16,MUC17,CSMD3,HMCN1,USH2 A,FAT3,DST,RYR2,NF1,TOP2 A,APOB,MACF1 and SYNE2.2.Based on GTEx database,the expression level of ABCB1 was the highest in normal adrenal tissue and the lowest in bone tissue.Compared with female,the expression of ABCB1 in male fat and breast tissue was significantly higher(P<0.05).Compared with male,the expression of ABCB1 in female brain tissue was significantly higher(P<0.05).3.Based on TCGA and GTEx database,the expression of ABCB1 in ovarian cancer was significantly lower than that in normal ovarian tissues(P<0.05).There was no significant difference in ABCB1 expression among patients with different stages of ovarian cancer.Theexpression level of ABCB1 was not related to the overall survival time of patients with ovarian cancer.Compared with the samples without mutation,there was no significant difference in the expression level of ABCB1 between the samples with ABCB1 mutation and those without mutation(P>0.05).4.Among the ovarian cancer patients who received first-line chemotherapy,the results of ABCB1 C3435 T test were: CC 14 cases(35.0%),CT 17 cases(42.5%),TT 9 cases(22.5%),CT+TT 26 cases(65.0%);ABCB1 G2677T/A test results: GG 11 cases(27.5%),GT 14 cases(35.0%),TT 15 cases),GT+TT 29 cases(72.5%).5.The risk of hematotoxicity in patients with ABCB1 C3435 T CT genotype and CT+TT was significantly lower than that in patients with CC genotype(OR=0.12,0.13;95% CI0.02~0.63,0.03~0.57;P<0.05).6.There was no correlation between the genotype of ABCB1 G2677T/A and hematotoxicity in patients ovarian cancer who received first-line chemotherapy(P>0.05).7.The genotypes of ABCB1 C3435 T and G2677T/A were not associated with gastrointestinal toxicity and nephrotoxicity in patients ovarian cancer who received first-line chemotherapy(P>0.05).8.The genotypes of ABCB1 C3435 T and G2677T/A were not correlated with the short-term efficacy of ovarian cancer patients receiving first-line chemotherapy(P>0.05).Conclusions1.There was no correlation between the expression level of ABCB1 in ovarian cancer and the stage and overall survival time of the patients.2.ABCB1 C3435 T polymorphism is associated with hematotoxicity in patients with ovarian cancer after receiving first-line chemotherapy,suggesting that ABCB1 C3435 T polymorphism may be a reliable molecular marker for predicting hematotoxicity in ovarian cancer patients receiving first-line chemotherapy.