结直肠癌患者化疗后CD4+T细胞表面NK相关受体表达水平动态变化及对预后的预测价值OA

Objective:To investigate dynamic changes of natural killer(NK)-related receptors on surface of CD4+T cells after chemotherapy in patients with colorectal cancer(CRC)and its prognostic value.Methods:A total of 251 CRC patients admitted to Hainan Cancer Hospital from February 2020 to March 2023 were selected as study objects.Peripheral blood samples of patients were collected,and expressions of NK-related receptors NKG2D and NKG2A on surface of CD4+T cells were detected by flow cytometry.According to prognosis,patients were divided into good prognosis group(n=154)and poor prognosis group(n=97).General data of two groups and expression of NK-related receptors on surface of CD4+T cells during chemotherapy were compared,and relationship between expression of NK-related receptors on surface of CD4+T cells and prognosis under different clinicopathological characteristics was analyzed.Generalized linear mixed effects models(GLMMs)was used to analyze relationship between expression of NK-related receptors on surface of CD4+T cells and prognosis.Unconditioned Logistic regression and restricted cubic spline model were used to analyze relationship between expression of NK-related receptors on surface of CD4+T cells and prognosis.Kaplan-Meier survival curve was used to verify effects of NK-related receptors NKG2D and NKG2A on survival of CRC patients.Results:Multivariate analysis of variance showed that NKG2D in good prognosis group was higher than poor prognosis group 1 to 6 months after treatment(t=9.260,P<0.001;t=6.490,P<0.001;t=10.594,P<0.001);NKG2A levels were lower than poor prognosis group(t=2.085,P=0.038;t=4.258,P<0.001;t=6.085,P<0.001);depth of tumor invasion,TNM stage,tumor differentiation degree,lymph node metastasis could not affect relationship between expression of NK-related receptors on CD4+T cells and prognosis(P>0.05).GLMMs analysis showed that the higher the expression of NKG2A,the lower the expression of NKG2D,the greater the risk of poor prognosis in CRC patients(P<0.001).Dose-response relationship showed that critical points of NKG2D and NKG2A and prognosis of CRC patients were 74.89%and 32.75%.When critical point was lower than that,NKG2D was positively correlated with risk of poor prognosis of CRC patients,while NKG2A was negatively correlated with risk of poor prognosis of CRC patients.Above critical point,NKG2D was negatively correlated with risk of poor prognosis in CRC patients,and NKG2A was positively correlated with risk of poor prognosis in CRC patients.Six-month survival rate was 42.60%in patients with low expression of NKG2D and 61.57%in patients with high expression of NKG2D.Six-month survival rate of patients with low expression of NKG2A was 56.45%,and 6-month survival rate of patients with high expression of NKG2A was 37.36%,with statistical difference between two groups(P<0.05).Conclusion:Expression of NKG2A is increased and expression of NKG2D is decreased after chemotherapy in CRC patients,imbalance of expression of NK-related receptors on surface of CD4+T cells inhibits killing function of cells,thus increasing risk of poor prognosis.