Objective To investigate the correlations between rs36084323, rs2227982, rs7421861 polymorphisms of programmed cell death-1 receptor (PD-1) and sensitivity to platinum-based chemotherapy in gastric cancer.
Methods One hundred and three gastric cancer patients were selected as study objects, and given two cycles of oxaliplatin plus tiggio (SOX) or cisplatin, paclitaxel plus 5-fluorouracil (PCF) chemotherapy. After chemotherapy, the patients were divided into sensitive group (45 cases) and resistant group (58 cases) according to RECIST 1.1 version of solid tumor efficacy evaluation criteria(RECIST). After chemotherapy, peripheral venous blood was collected, and the polymorphism of rs36084323, rs2227982 and rs7421861 of PD-1 gene was detected by the TaqMan probe single nucleotide polymorphism (SNP) genotyping technique, and the relationship between the polymorphism and the susceptibility of patients with gastric cancer to platinum chemotherapy was analyzed.
Results The genotype frequency distribution of rs36084323, rs2227982 and rs7421861 of PD-1 gene complied with Hardy-Weinberg equilibrium law (P>0.05). The genotype and allele distribution of PD-1 locus rs2227982 and rs7421861 in the sensitive group and the resistant group showed significant differences(P < 0.05). The sensitive of TT genotype of allele T(OR=1.739, 95%CI, 1.656 to 1.867)and CT genotype(OR=1.524, 95%CI, 1.435 to 1.663)to chemotherapy and were significantly higher than that of CC genotype and C allele (P < 0.05). T allele had higher sensitivity to chemotherapy than C allele (OR=1.721, 95%CI, 1.603 to 1.851), and the difference was statistically significant (P < 0.05). TT genotype (OR=1.605, 95%CI, 1.556 to 1.767) and CT genotype (OR=1.414, 95%CI, 1.372 to 1.525) of rs7421861 had lower sensitivity to chemotherapy than CC genotype, and T allele had lower sensitivity to chemotherapy than C allele (OR=1.531, 95% CI, 1.423 to 1.672), and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that the degree of differentiation, rs2227982 polymorphism and rs7421861 polymorphism of PD-1 gene were significantly correlated with the sensitivity to platinum chemotherapy in gastric cancer patients (P < 0.01).
Conclusion The polymorphism of rs2227982 and rs7421861 locus of PD-1 gene may be related to the sensitivity of patients with gastric cancer to platinum chemotherapy, and the individuals carrying the T allele of rs2227982 have better response to platinum chemotherapy, and the individuals carrying the C allele of rs7421861 have poor response to platinum chemotherapy.
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