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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1498524
This article is part of the Research Topic Early-Onset Lung Cancer: Global Trends, Disparities, and Personalized Treatment Strategies View all articles
Characterizing Microbial Communities and Their Correlation with Genetic Mutations in Early-Stage Lung Adenocarcinoma: Implications for Disease Progression and Therapeutic Targets
Provisionally accepted- China-Japan Friendship Hospital, Beijing, Beijing Municipality, China
Background:Lung adenocarcinoma (LUAD), the most prevalent form of lung cancer.The transition from adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) to invasive adenocarcinoma (IAC) is not fully understood.Intratumoral microbiota may play a role in LUAD progression, but comprehensive stage-wise analysis is lacking.Methods:Tumor and bronchoalveolar lavage fluid (BALF) samples from patients with AIS/MIA or IAC were collected for next-generation sequencing to characterize microbial diversity and composition. DNA extraction involved lysing samples with nuclease and protease, followed by homogenization and elution. Sequencing libraries were prepared and sequenced on the Illumina platform. Whole exome sequencing was performed to identify somatic mutations and genetic variants. Bioinformatics analysis, including taxonomic annotation with Kraken2 and de novo assembly with MEGAHIT, was conducted to process metagenomic data. Correlation analysis was performed to link microbial species with mutated genes using custom R scripts.Results: Metagenomic analysis revealed a distinct microbial profile in IAC compared to AIS/MIA, with increased abundance of Bacteroidetes and Firmicutes in the IAC group. Bosea sp. and Microbacterium paludicola, were less abundant in IAC, suggesting a potential protective role in early-stage disease. Conversely, Mycolicibacterium species were more prevalent in IAC, indicating a possible contribution to disease progression. Genetic sequencing identified PTPRZ1 strongly correlating with microbial composition, suggesting a mechanistic link between microbiota and genetic alterations in LUAD.This study characterizes microbial communities in various stages of LUAD, revealing links between microbiota and genetic mutations. The unique microbiota suggests its role in LUAD progression and as a therapeutic target.
Keywords: Lung Adenocarcinoma, tumor microbiome, PTPRZ1, Next-generation sequencing, therapeutic targets
Received: 19 Sep 2024; Accepted: 13 Dec 2024.
Copyright: © 2024 Yang, Zhang, Feng, Qi, Kong, Zhu, Liang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hongxiang Feng, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
Fei Qi, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
Fanjia Kong, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
Weijie Zhu, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
Zhenrong Zhang, China-Japan Friendship Hospital, Beijing, 100029, Beijing Municipality, China
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