The value of second-generation gene sequencing in lung cancer immunotherapy with concurrent infections

BMC Cancer. 2025 Oct 23;25(1):1636. doi: 10.1186/s12885-025-15045-4.

Abstract

Objective: To collect clinical baseline data of patients with lung cancer and infection, explore the association between clinical characteristics and infection characteristics between the immunotherapy group and the non-immunotherapy group. At the same time, analyze the distribution of pathogens in patients, compare whether there are differences in pathogen distribution between the two groups, and thus explore the diagnostic value of metagenomic next-generation sequencing for patients with lung cancer immunotherapy and infection.

Methods: A total of 107 patients with lung cancer and infection treated at Jingzhou First People’s Hospital from December 2022 to July 2025 were included in the study. They were divided into an immunotherapy group (40 cases) and a non-immunotherapy group (67 cases) based on whether they received immunotherapy. All patients underwent electronic bronchoscopy and mNGS testing. The pathogen detection results and various clinical baseline information of the enrolled patients were collected to explore the association between infection characteristics and clinical characteristics in the two groups and to compare whether there were differences in pathogen distribution between the two groups.

Results: In terms of clinical manifestations, the proportion of patients with fever was higher in the immunotherapy group than in the non-immunotherapy group. The length of hospital stay and hospitalization costs were higher in the immunotherapy group than in the non-immunotherapy group, with statistically significant differences (P < 0.05). In terms of laboratory indicators, patients in the immunotherapy group had higher levels of D-dimer and inflammatory markers (CRP, PCT, IL-6) than those in the non-immunotherapy group, while albumin and hemoglobin levels were lower, with statistically significant differences (P < 0.05). In the immunotherapy group, 11 cases of pure bacterial infection, 0 cases of pure fungal infection, 2 cases of pure viral infection, and 25 cases of mixed infection were detected. In the non-immunotherapy group, there were 5 cases of pure bacterial infection, 6 cases of pure fungal infection, 1 case of pure viral infection, and 51 cases of mixed infection. We found that the detection rate of pure bacterial infection was higher in the immunotherapy group than in the non-immunotherapy group (X² = 7.907, P = 0.005 < 0.05), with the tuberculosis bacillus infection rate significantly higher in the immunotherapy group than in the non-immunotherapy group (X² = 5.738, P = 0.017 < 0.05). Among mixed infections, the detection rate of fungal mixed infections was higher in the immunotherapy group than in the non-immunotherapy group (X² = 7.474, P = 0.006 < 0.05). with the immunotherapy group showing significantly higher infection rates for Pneumocystis jirovecii (X² = 4.292, P = 0.038 < 0.05) and Aspergillus terreus (X² = 4.485, P = 0.034 < 0.05) compared to the non-immunotherapy group, with statistically significant differences. The detection rate of mixed bacterial infections in the non-immunotherapy group was higher than that in the immunotherapy group (X² = 8.568, P = 0.003 < 0.05). The detection rates of single bacterial and viral infections, as well as other mixed infections, in the immunotherapy group were not significantly different from those in the non-immunotherapy group (P > 0.05).

Conclusion: The incidence of bacterial infections and mixed fungal infections increased in lung cancer patients after immunotherapy. Among them, the detection rates of Mycobacterium tuberculosis, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly higher in the immunotherapy group than in the non-immunotherapy group. The detection rate of bacterial mixed infections was higher in the non-immunotherapy group than in the immunotherapy group. In the immunotherapy group, bacterial infections were primarily caused by Mycobacterium tuberculosis and Streptococcus pneumoniae, fungal infections were primarily caused by Aspergillus fumigatus and Pneumocystis jirovecii, and viral infections were primarily caused by Epstein-Barr virus (EBV). In the non-immunotherapy group, bacterial infections were primarily caused by Pseudomonas aeruginosa and Haemophilus influenzae, fungal infections were primarily caused by Aspergillus fumigatus, Pneumocystis jirovecii, and Aspergillus flavus, and viral infections were primarily caused by EB virus and influenza A virus H1N1. Additionally, mNGS demonstrated good applicability in the population undergoing immunotherapy for lung cancer and had a significant impact on treatment outcomes.

Keywords: Immunotherapy; Lung cancer; Metagenomic second-generation sequencing; Pathogen detection; Pulmonary infection.