| Objective: Through META analysis and bioinformatics analysis,search for reliable predictive markers that affect the efficacy of platinum drugs,guide individualized treatment of tumor patients,and improve the effectiveness and safety of platinum drugs in anti-tumor treatment.Methods: In this Meta analysis and bioinformatics data analysis,31 qualified studies are included,including Oncomines(https://www.oncomine)and GENT(http://medical-genome.kribb.re.kr/GENT)And gene expression Omnibus(GEO)datasets and other online tools for prognosis and gene expression analysis.In addition,the association between DNA repair gene expression and prognosis is assessed by using a data set(PRECOG,http://precog.stanford.edu)that can be used to predict the clinical outcome of the genome map.In addition,the c Bio Portal tool based on the TCGA data set is used to analyze the changes of these DNA repair genes,including mutations,fusions,amplifications,and deep deletions.Results: 1.The MTHFR A1298 C polymorphism is related to the efficacy of platinum-based chemotherapeutics in patients with colorectal cancer.In the allele model,compared with the A allele,the C allele increases the resistance of platinum-based chemotherapeutics.Drug resistance [OR(95%CI)= 1.862(1.144-3.031),P = 0.012 ];in the recessive gene model,the CC genotype increased the resistance of platinum-based chemotherapeutics compared with the AA/AC genotype [OR(95%CI)= 2.441(1.301-4.579),P = 0.005],in the heterozygous gene model,the AC genotype increased the resistance of platinum chemotherapeutics compared with the AA genotype [OR(95 %CI)= 2.361(1.243-4.483),P = 0.009];2.The MDR1 C1236 T polymorphism is related to the resistance of the Asian population to platinum-based chemotherapeutics.Five models show that the occurrence of C1236 T site mutations can reduce the Asian population Resistance to platinum-based chemotherapeutics [allele model T VS.C: OR(95% CI)= 0.680(0.525-0.881),P =0.003;dominant gene model TT VS.TC / CC: OR(95 % CI)= 0.610(0.414-0.899),P = 0.013;recessive gene model TT / TC VS.CC: OR(95% CI)= 0.641(0.418-0.981),P = 0.041;homozygous gene model TT VS CC: OR(95% CI)= 0.514(0.309-0.856),P = 0.011;heterozygous gene model TC VS.CC: OR(95% CI)=0.766(0.480-1.221),P = 0.262](Table 3 and Figure 2D);3.MDR1 C3435 T polymorphism is correlated with the efficacy of platinum-based chemotherapeutics in patients with non-small cell lung cancer.In the allele model,the T allele is reduced compared to the C allele The resistance of platinum chemotherapeutics [OR(95%CI)= 0.663(0.448-0.982),P = 0.040],in the recessive gene model,the TT genotype reduced platinum compared with the CC/CT genotype Chemotherapeutic drug resistance [OR(95% CI)= 0.580(0.360-0.935),P = 0.025].In the homozygous gene model,the TT genotype reduced the resistance of platinum chemotherapeutics compared with the CC genotype.Pharmacological properties [OR(95% CI)= 0.462(0.259-0.824),P = 0.009],in heterozygous genes In the model,the CT genotype reduced the resistance of platinum-based chemotherapeutics compared with the CC genotype [OR(95% CI)= 0.634(0.416-0.965),P = 0.033],and the remaining sites were in the 5 models In the analysis,it was shown that there was no significant correlation with drug resistance;among 4,33 cancers,the expression levels of MDR1 and MTHFR genes were lower,and the expression levels of ERCC1 gene were higher.The expression of ERCC1 gene is significantly increased in cancer tissues of patients with blood cancer,lymphoma,and myeloma.The expression of MDR1 gene is only significantly increased in blood cancer patients,and the expression level of MDR1 gene is significantly reduced in lung squamous cell carcinoma and breast cancer.MTHFR is in lung cancer.The expression level is significantly reduced,and there is no significant difference between normal tissues and cancer tissues in colorectal cancer;5.In the chip GSE4573,the overall survival rate(OS)of lung cancer patients with low expression of the MDR1 gene is significantly reduced(Log-rank test: P<0.0001,HR = 0.60,95% CI = 0.37-0.97),the overall survival rate(OS)of colorectal cancer patients with low expression of the MTHFR gene in the chips GSE17536 and GSE24550 was significantly reduced(Log-rank test: P <0.0001,HR = 0.40,95% CI= 0.24-0.65;P <0.0001,HR = 0.21,95% CI = 0.04-0.99),the overall survival rate(OS)of lung cancer patients with high expression of ERCC1 in the chip GSE19188 and chip GSE29013 was significantly reduced(Log-Rank test: P <0.0001,HR = 2.93,95% CI = 1.25-6.90;P <0.0001,HR = 7.52,95% CI = 0.92-61.48);the total genetic change level of 6,3 candidate genes is only 1.3 %-9% range,but there are high levels of repetitive polymorphisms or somatic mutations,such as missense mutations,fusion mutations,and deep deletions.The frequency of changes in 33 cancers is high,especially melanoma and cervical cancer More than 15%,the 3 genes have higher mutations in different protein domains.Conclusion: The results of the study showed that Asian tumor patients with MDR1C1236 T mutation and non-small cell lung cancer patients with MDR1 C3435 T mutation are sensitive to platinum-based chemotherapy drugs,and colorectal cancer patients with MTHFR A1298 C mutation are resistant to platinum The invisible model and homozygous model of ERCC1 C8092 A show that this site mutation can increase the sensitivity of patients to platinum drugs.Bioinformatics analysis confirmed that,in 19 cancers,the expression level of MDR1 and MTHFR genes was low,and the expression level of ERCC1 gene was high.Subsequent results showed that the increase of ERCC1 gene expression level or the decrease of MDR1 gene expression level has no effect on non-small cells.The prognosis of patients with lung cancer has a poorer effect,and the low expression of MTHFR gene has a poorer effect on the prognosis of patients with colorectal cancer. |
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