关键词: 非小细胞肺癌, PD-1抑制剂, DNA甲基化

Abstract:

Objective To investigate the association between the promoter DNA methylation of RUNX3， P16， and DAPK genes and the efficacy of programmed death receptor-1 （PD-1） inhibitors in patients with non-small cell lung cancer （NSCLC）. Methods A total of 73 patients with who NSCLC received treatment with PD-1 inhibitors in our hospital from January 2020 to January 2024 were recruited. These patients were then divided into a disease progression group （characterized by progressive disease） and a disease control group （comprising patients with complete response， partial response， and stable disease） based on the therapeutic response. The promoter DNA methylation status of the RUNX3， P16， and DAPK genes in peripheral blood samples， tumor markers， and pulmonary CT features were compared between the two groups. The influencing factors for the sustained disease progression after PD-1 inhibitor therapy were analyzed. Results Among the 73 patients， 4 achieved a complete response， 29 achieved a partial response， 25 had a stable disease state， and 15 experienced disease progression. The proportion of PD-L1-positive cases was significantly higher in the disease control group compared to that in the disease progression group （P < 0.05）. The expression levels of RUNX3， P16， and DAPK were significantly higher in the disease control group than those in the disease progression group （P < 0.05）. No statistically significant differences were detected between the two groups in CT features such as lesion density， lesion margin， pleura relationship， vascular signs， ground-glass opacity， calcification， or distal obstructive inflammation （P > 0.05）. The serum levels of carcinoembryonic antigen （CEA）， neuron-specific enolase （NSE）， cytokeratin 19 fragment （CYFRA21-1）， and cancer antigen 125 （CA125） showed no significant differences between the groups （P > 0.05）. Logistic multivariate regression analysis indicated that RUNX3 （OR = 0.257， 95%CI： 0.103 - 0.644）， P16 （OR = 0.243， 95%CI： 0.096 - 0.608）， DAPK （OR = 0.217， 95%CI： 0.087 - 0.543）， and PD-L1 positivity （OR = 0.242， 95%CI： 0.096 - 0.607） were independent influencing factors for sustained disease progression in NSCLC patients after PD-1 inhibitor therapy （P < 0.05）. Conclusions Promoter DNA methylation of RUNX3， P16， and DAPK is significantly associated with the efficacy of PD-1 inhibitors in the treatment of NSCLC. Moreover， a hypomethylation status is correlated with more favorable therapeutic responses in patients.

Key words: non-small cell lung cancer, PD-1 inhibitor, DNA methylation