The predictive value of the epithelial cell proliferation pathway genes for the prognosis of elderly non-small cell lung cancer patients receiving immunotherapy / 中华老年医学杂志

ABSTRACT

Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS 10.9 months vs.17.1 months, HR=1.84, 95% CI 1.09-3.08, P<0.05; mPFS 2.8 months vs.4.2 months, HR=1.58, 95% CI 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.