Relationship and interaction between tissue delta-like ligand 3 expression and xeroderma pigmentosum gene G gene polymorphism and sensitivity to platinum-based chemotherapy in advanced squamous lung cancer / 中国医师进修杂志

ABSTRACT

Objective:To analyze the interaction of tissue delta-like ligand 3 (DLL3) expression and xeroderma pigmentosum gene G (XPG) gene polymorphism on the sensitivity of advanced lung squamous cell carcinoma to platinum-based chemotherapy.Methods:One hundred and forty patients with advanced squamous lung cancer admitted to Yuechi County People′s Hospital from March 2019 to December 2021 were selected and all were given carboplatin and paclitaxel for injection (albumin-bound) in a fully informed manner, with one cycle every 3 weeks for a total of 4 cycles of treatment. The patients were divided into sensitive group (46 cases) and non-sensitive group (94 cases) according to their sensitivity to chemotherapy. Baseline information, tissue DLL3 expression and XPG gene polymorphism were compared between the two groups, and tissue DLL3 expression in patients with different XPG genotypes was compared. Multi-factor Logistic regression analysis was used to analyzed the factors associated with the sensitivity to chemotherapy, and interaction coefficient γ was used to analyze tissue DLL3 expression and XPG.Results:The tissue DLL3 expression score of the sensitive group was lower than that in the non-sensitive group: (3.28 ± 0.93) scores vs. (7.59 ± 1.22) scores, there was statistical difference ( P<0.01). The patients with CC genotype in the sensitive group were more than those in the non-sensitive group, and the patients with CT and TT genotypes were less than those in the non-sensitive group ( P<0.05). Tissue DLL3 expression score in patients with CC, CT, TT genotype were (3.51 ± 0.93), (6.76 ± 1.08), (10.09 ± 1.12) scores, there was statistical difference ( P<0.05); and tissue DLL3 expression score was CC<CT<TT genotype, there were significant differences between pairwise comparisons ( P<0.05). Multivariate Logistic regression analysis showed that the probability of insensitivity to platinum chemotherapy in patients with high tissue DLL3 expression was 8.368 times than that of patients with low expression, and the probability of insensitivity to platinum chemotherapy in patients with XPG genotype CT and TT was 5.349 and 9.517 times higher than that in CC genotype. The OR value caused by DLL3 alone was 6.222, the OR value caused by XPG gene polymorphism alone was 56.000, and the OR value caused by the coexistence of the two was 275.333, and the interaction coefficient γ = 1.396, indicated that the expression of tissue DLL3 was related to XPG gene polymorphism. The effect of sex had a positive interaction, and the OR value of the interaction between the two was less than the product of the OR value of the two independent factors. The model representing the interaction effect of tissue DLL3 expression and XPG gene polymorphism on chemotherapy sensitivity was a submultiplicative model. Conclusions:Patients with advanced squamous lung cancer of the CC genotype at the XPG C46T locus are more sensitive to platinum-based chemotherapy than patients of the CT and TT types, and are associated with platinum-based chemotherapy responsiveness. High tissue DLL3 expression has a positive interaction with the effect of the XPG gene polymorphism, and the two are consistent with a submultiplicative model, which may be a genetic mechanism for poor response to platinum-based chemotherapy.