To analyze the predictive significance of receptor interacting protein kinase 2 (RIPK2) and programmed death-1 (PD-1) expression in the efficacy of immunotherapy for lung cancer patients.

Seventy-nine lung cancer patients receiving immunotherapy at Cangzhou People′s Hospital from January 2020 to December 2024 were selected. Clinical data were collected; RIPK2 and PD-1 mRNA expression levels were detected by quantitative real time polymerase chain reaction; RIPK2 and PD-1 protein expression levels were measured by immunohistochemistry; therapeutic efficacy was evaluated. Based on follow-up results, 52 patients were classified as effective (significant efficacy) and 27 as ineffective (poor efficacy or death).

RIPK2 mRNA (1.62±0.37 vs. 1.00±0.24), PD-1 mRNA (1.38±0.34 vs. 1.00±0.19), RIPK2 protein high-expression rate (72.15% vs. 51.90%), and PD-1 protein high-expression rate (69.62% vs. 53.16%) in lung cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Significant differences were observed between effective and ineffective groups in eastern cooperative oncology group (ECOG) score, maximum tumor diameter, epidermal growth factor receptor (EGFR) mutation, number of metastatic sites, liver metastasis, and treatment line (P<0.05). The ineffective group exhibited higher standardized uptake value max (SUVmax) (10.34±1.89 vs. 6.15±1.76), metabolic tumor volume (MTV) (22.87±4.85 vs. 16.29±4.41 cm³), total lesion glycolysis (TLG) (96.14±11.64 vs. 80.35±10.32 g/ml), and abdominal CT abnormality rate (70.37% vs. 19.23%) compared to the effective group (P<0.05). RIPK2 mRNA (1.45±0.32 vs. 1.98±0.41), PD-1 mRNA (1.18±0.34 vs. 1.83±0.49), and protein high-expression rates (RIPK2: 63.46% vs. 88.89%; PD-1: 59.62% vs. 88.89%) in the effective group were lower than those in the ineffective group (P<0.05). Receiver operating characteristic curve (ROC) analysis revealed area under curve (AUC) values of 0.888, 0.877, and 0.952 for RIPK2 mRNA, PD-1 mRNA, and their combination in predicting efficacy, respectively (P<0.05). Patients with high RIPK2 expression showed significantly lower survival rates (28.57% vs. 42.86%) and progression-free survival rates (16.67% vs. 25.00%), while those with high PD-1 expression had lower survival rates (33.33% vs. 40.00%) and progression-free survival rates (20.83% vs. 22.00%) compared to low-expression groups (P<0.05).

High expression of RIPK2 and PD-1 combined with imaging metabolic parameters can predict the efficacy and prognosis of immunotherapy in lung cancer, with patients exhibiting low expression achieving better survival benefits.