Metagenomic Next-generation Sequencing for Lung Cancer Low Respiratory Tract Infections Diagnosis and Characterizing Microbiome Features

Overview

Journal Front Cell Infect Microbiol

Date 2025 Feb 7

PMID 39916938

Authors

Yao Liu

Bohan Yang

Qi Qi

Shijie Liu

Yiheng Du

Linlin Ye

Qiong Zhou

Affiliations

Soon will be listed here.

Abstract

Background: The capability of mNGS in diagnosing suspected LRTIs and characterizing the respiratory microbiome in lung cancer patients requires further evaluation.

Methods: This study evaluated mNGS diagnostic performance and utilized background microbial sequences to characterize LRT microbiome in these patients. GSVA was used to analyze the potential functions of identified genera.

Results: Bacteria were the most common pathogens (n=74) in LRTIs of lung cancer patients, and polymicrobial infections predominated compared to monomicrobial infections (p<0.001). In diagnosing LRTIs in lung cancer patients, the pathogen detection rate of mNGS (83.3%, 70/84) was significantly higher than that of sputum culture (34.5%, 29/84) (p<0.001). This result was consistent with that of non-lung cancer patients (p<0.001). Furthermore, in the specific detection of bacteria (95.7% vs. 22.6%) and fungi (96.0% vs. 22.2%), the detection rate of mNGS was also significantly higher than that of CMTs mainly based on culture (p<0.001, p<0.001). However, in the detection of CMV/EBV viruses, there was no significant difference between the detection rate of mNGS and that of viral DNA quantification (p = 1.000 and 0.152). mNGS analysis revealed , , , , and as the most prevalent genera in the LRT of lung cancer patients. GSVA revealed significant correlations between these genera and tumor metabolic pathways as well as various signaling pathways including PI3K, Hippo, and p53.

Conclusion: mNGS showed a higher pathogen detection rate than culture-based CMTs in lung cancer patients with LRTIs, and also characterizing LRT microbiome composition and revealing potential microbial functions linked to lung carcinogenesis.

References

Liu H, Tao L, Zhang J, Zhu Y, Zheng Y, Liu D . Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. Int J Cancer. 2017; 142(4):769-778. DOI: 10.1002/ijc.31098. View

Zhu W, Shen W, Wang J, Xu Y, Zhai R, Zhang J . Capnocytophaga gingivalis is a potential tumor promotor in oral cancer. Oral Dis. 2022; 30(2):353-362. DOI: 10.1111/odi.14376. View

Liu L, Yuan M, Shi Y, Su X . Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumonia and Colonisation. Front Cell Infect Microbiol. 2022; 11:784236. PMC: 8727434. DOI: 10.3389/fcimb.2021.784236. View

Sepich-Poore G, Zitvogel L, Straussman R, Hasty J, Wargo J, Knight R . The microbiome and human cancer. Science. 2021; 371(6536). PMC: 8767999. DOI: 10.1126/science.abc4552. View

Peng J, Du B, Qin H, Wang Q, Shi Y . Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients. J Infect. 2021; 82(4):22-27. DOI: 10.1016/j.jinf.2021.01.029. View

Li N, Cai Q, Miao Q, Song Z, Fang Y, Hu B . High-Throughput Metagenomics for Identification of Pathogens in the Clinical Settings. Small Methods. 2021; 5(1):2000792. PMC: 7883231. DOI: 10.1002/smtd.202000792. View

Huang D, Su X, Yuan M, Zhang S, He J, Deng Q . The characterization of lung microbiome in lung cancer patients with different clinicopathology. Am J Cancer Res. 2019; 9(9):2047-2063. PMC: 6780665. View

Schloss P, Handelsman J . Biotechnological prospects from metagenomics. Curr Opin Biotechnol. 2003; 14(3):303-10. DOI: 10.1016/s0958-1669(03)00067-3. View

Chiu C, Miller S . Clinical metagenomics. Nat Rev Genet. 2019; 20(6):341-355. PMC: 6858796. DOI: 10.1038/s41576-019-0113-7. View

10.

Murphy C, Fowler R, Balada-Llasat J, Carroll A, Stone H, Akerele O . Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection. J Clin Microbiol. 2020; 58(7). PMC: 7315029. DOI: 10.1128/JCM.00128-20. View

11.

Kim J, Hong S, Kim E . Capnocytophaga sputigena bacteremia in a patient with chronic lymphocytic leukemia. Ann Lab Med. 2014; 34(4):325-7. PMC: 4071192. DOI: 10.3343/alm.2014.34.4.325. View

12.

Sun L, Zhang S, Yang Z, Yang F, Wang Z, Li H . Clinical Application and Influencing Factor Analysis of Metagenomic Next-Generation Sequencing (mNGS) in ICU Patients With Sepsis. Front Cell Infect Microbiol. 2022; 12:905132. PMC: 9326263. DOI: 10.3389/fcimb.2022.905132. View

13.

Liu B, Beck E, Fisher M . The Brief Case: Ventilator-Associated Corynebacterium accolens Pneumonia in a Patient with Respiratory Failure Due to COVID-19. J Clin Microbiol. 2021; 59(9):e0013721. PMC: 8372998. DOI: 10.1128/JCM.00137-21. View

14.

Wang H, Hu J, Wu J, Ji P, Shang A, Li D . The Function and Molecular Mechanism of Commensal Microbiome in Promoting Malignant Progression of Lung Cancer. Cancers (Basel). 2022; 14(21). PMC: 9658664. DOI: 10.3390/cancers14215394. View

15.

Ramirez-Labrada A, Isla D, Artal A, Arias M, Rezusta A, Pardo J . The Influence of Lung Microbiota on Lung Carcinogenesis, Immunity, and Immunotherapy. Trends Cancer. 2020; 6(2):86-97. DOI: 10.1016/j.trecan.2019.12.007. View

16.

Mo H, Wei Q, Zhong Q, Zhao X, Guo D, Han J . Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway. Int J Mol Sci. 2022; 23(14). PMC: 9324654. DOI: 10.3390/ijms23147853. View

17.

Nie H, Ju H, Fan J, Shi X, Cheng Y, Cang X . O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nat Commun. 2020; 11(1):36. PMC: 6946671. DOI: 10.1038/s41467-019-13601-8. View

18.

Kim O, Choi B, Kim D, Kim N, Rho J, Sul W . The microbiome of lung cancer tissue and its association with pathological and clinical parameters. Am J Cancer Res. 2022; 12(5):2350-2362. PMC: 9185621. View

19.

Mandell L, Wunderink R, Anzueto A, Bartlett J, Campbell G, Dean N . Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2:S27-72. PMC: 7107997. DOI: 10.1086/511159. View

20.

Derosa L, Hellmann M, Spaziano M, Halpenny D, Fidelle M, Rizvi H . Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018; 29(6):1437-1444. PMC: 6354674. DOI: 10.1093/annonc/mdy103. View