A Novel nor@DHB Matrix for Direct Microbial Analysis in Lung Cancer Tissues.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published Date: Jun 25, 2025

Abstract

Dynamic changes occurring in the lung microbiota can impact the initiation, progression, and prognosis of lung cancer (LC). Consequently, the development of suitable intratumoral microbiota analysis methods is crucial. Although matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) involves straightforward operations and provides precise results, the "direct smear method" limits the identification of bacterial subspecies. Furthermore, the issue of inadequate quantification with MALDI MS renders it unsuitable for direct analysis of intratumoral bacteria. To address these challenges, a novel ionic liquid in this study is employed, called norharmane conjugated to 2,5-dihydroxybenzoic acid (Nor@DHB) for the direct detection of intratumoral bacteria using MALDI MS. Because gram-negative bacteria are dominant within cancer cells, lipid A is selected as the chemical fingerprint for bacterial identification. The results demonstrated that using Nor@DHB can enhance the lipid A signal by an order of magnitude and achieved a good linear relationship within a concentration range of 0.01-80 ng mL. Here, this method is successfully applied to the direct analysis of lipid A in actual clinical samples. Subsequent machine learning and nomogram models further confirmed the correlation between characteristic lipid A ions and LC patient clinicopathological features, which are further validated through both in vitro and in vivo experiments.

Authors

  • Liang Shan
    Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Xin Xu
    State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
  • Lin Huang
    Division of Vascular Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510800, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • Dan Li
    State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China.
  • Yiran Deng
    Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Xiangfei Xue
    Shanghai Institute of Thoracic oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Susu Guo
    Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Yiman Huang
    Shanghai Institute of Thoracic oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Xiao Zhang
    Merck & Co., Inc., Rahway, NJ, USA.
  • Yongchun Yu
    Institutes of Brain Sciences, FuDan University, Shanghai, 200433, China.
  • Lifang Ma
    Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, No. 241, West Huaihai Road, Shanghai, 200030, P. R. China.
  • Kun Qian
    Key Laboratory of Brain Health Intelligent Evaluation and Intervention (Beijing Institute of Technology), Ministry of Education, Beijing, China.
  • Jiayi Wang
    Department of Statistics, Texas A&M University.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals