Correlation Between Single Nucleotide Polymorphisms Of Pd-l1 And Survival Prognosis Of Patients With Colorectal Cancer After Adjuvant Chemotherapy

Background and ObjectiveColorectal cancer(CRC)is a common malignant tumor of the digestive tract,and the number of new cases per year ranks fourth in malignant tumors worldwide.In China,the morbidity and mortality of colorectal cancer have been on the rise,and most patients are in advanced stage at the time of initial diagnosis,losing the chance of surgery and having a poor prognosis.For patients with stage III and stage II with high risk factors,surgery is mainly combined with postoperative adjuvant chemotherapy.The chemotherapy regimen is mainly based on 5-FU.Studies have shown that capecitabine-based adjuvant chemotherapy significantly reduces the risk of postoperative recurrence in patients with colorectal cancer.Therefore,adjuvant chemotherapy for colorectal cancer is mainly based on capecitabine-based chemotherapy.The PD-L1 gene is located on chromosome 9p24.1 and contains eight exons.It has been reported in the literature that there are multiple SNP loci in the 3'-untranslated region(3'-UTR)of PD-L1,among which the microRNA(miRNA)binding site rs2297136(C> T)in the 3'-UTR region of PD-L1 gene have been proved to be related to disease invasion and poor survival rate.It has been reported that the PD-L1 gene polymorphism locus rs2297136(C>T)is associated with higher risk of HCC and is associated with poor prognosis in non-small cell lung cancer.The PD-L1 gene rs2297136(C>T)was located in the intron region of the gene.The sequencing results of the PD-L1 SNP locus showed that the rs2297136(C>T)locus contained the rs2297136(C>T)CC genotype? rs2297136(C>T)CT genotype? rs2297136(C>T)TT genotype.However,the relationship between PD-L1 gene polymorphism and survival and prognosis of postoperative adjuvant chemotherapy in patients with colorectal cancer remains unclear.This site was selected to investigate the relationship between the genetic variation of different genotypes of PD-L1 and the survival prognosis of colorectal cancer surgery combined with capecitabine adjuvant chemotherapy to better guide the clinical.Information and methodsThe study included 265 patients with colorectal cancer diagnosed by histopathology at the First Affiliated Hospital of Zhengzhou University.All of these patients underwent colorectal cancer resection and received capecitabine-based adjuvant chemotherapy.The clinical pathological data obtained through the electronic medical record,including the degree of tumor differentiation of the tumor,the tumor site,the TNM staging of the postoperative pathology,and the treatment plan.The TNM staging was assessed according to the intestinal cancer staging standard set by the eighth edition of AJCC.Allele amplification method was used to determine the genotyping of PD-L1 gene marker polymorphism locus in serum,and real-time quantitative fluorescence PCR was used to detect the expression level of PD-L1 gene mRNA in cancer tissues.The method of collating the analytical data is as follows: the correlation between the genotype of the PD-L1 gene polymorphism locus and other variables is analyzed by chi-square test or non-parametric test,and univariate and multivariate analysis was conducted by Cox model to determine independent prognostic factors.The mRNA expression of PD-L1 gene in patients with different genotypes was analyzed by rank-sum test.Kaplan-meier survival analysis was used to draw the survival curve and analyze the survival difference.Results1.In terms of efficacy data,265 patients included in this study were able to evaluate the efficacy after treatment.According to follow-up analysis,overall disease free survival(DFS)and overall survival(OS)were 4.6 years and 6.5 years respectively.2.The frequency of allele distribution in colorectal cancer patients included in the study was: homozygous TT type 185 cases(69.81%),CC type 8 cases(3.02%),heterozygous TC type 72 cases(27.17%).When comparing the prognosis of patients,because the number of patients with CC genotype was relatively small,statistical analysis was performed on these patients and heterozygous TC patients and combined analysis,and there was no significant difference in the distribution of baseline clinical data between the two groups of genotype patients.The median DFS of homozygous TT genotype and TC/CC genotype patients were 4.8 years and 3.5 years respectively,with statistically significant difference(P=0.0047).The median OS of the two genotypes was 6.7 years and 4.7 years,respectively,with significant statistical differences(P < 0.0001).3.The Cox risk ratio model was used for analysis.Univariate analysis showed that age,ECOG score,tumor stage,and rs2297136(C>T)genotype loci were all influencing factors of OS.Multivariate analysis showed: rs2297136(C> T Genotype locus,ECOG score,and pathological stage were independent prognostic factors of OS(HR=1.91,P=0.007).4.The mRNA expression of PD-L1 was measured in 89 patients with cancer tissues.In the analysis,the mRNA expression level of PD-L1 in TC/CC patients was significantly higher than that in TT genotypes.The statistical difference was significant.Significance(P < 0.001).The median value of PD-L1 mRNA expression was used as a threshold,and PD-L1 expression was divided into high-expression patient group(45 cases)and low-expression patient group(44 cases).PD-L1 high expression group patients had lower OS.The patient group was under-represented and the difference was statistically significant(P=0.045).Conclusion1.Patients with the TC/CC genotype carrying the C allele at the PD-L1 gene rs2297136(C>T)locus had poor DFS and OS compared to TT patients.2.The prognosis of colorectal cancer patients receiving capecitabine-based adjuvant chemotherapy may be different.It may be the PD-L1 gene rs2297136(C>T)site,which affects the prognosis of patients by mediating the expression of PD-L1 mRNA.