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Prognostic model based on B cell marker genes for NSCLC patients under neoadjuvant immunotherapy by integrated analysis of single-cell and bulk RNA-sequencing data

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Abstract

Background

Neoadjuvant immunotherapy has evolved as an effective option to treat non-small cell lung cancer (NSCLC). B cells play essential roles in the immune system as well as cancer progression. However, the repertoire of B cells and its association with clinical outcomes remains unclear in NSCLC patients receiving neoadjuvant immunotherapy.

Methods

Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data for LUAD samples were accessed from the TCGA and GEO databases. LUAD-related B cell marker genes were confirmed based on comprehensive analysis of scRNA-seq data. We then constructed the B cell marker gene signature (BCMGS) and validated it. In addition, we evaluated the association of BCGMS with tumor immune microenvironment (TIME) characteristics. Furthermore, we validated the efficacy of BCGMS in a cohort of NSCLC patients receiving neoadjuvant immunotherapy.

Results

A BCMGS was constructed based on the TCGA cohort and further validated in three independent GSE cohorts. In addition, the BCMGS was proven to be significantly associated with TIME characteristics. Moreover, a relatively higher risk score indicated poor clinical outcomes and a worse immune response among NSCLC patients receiving neoadjuvant immunotherapy.

Conclusions

We constructed an 18-gene prognostic signature derived from B cell marker genes based on scRNA-seq data, which had the potential to predict the prognosis and immune response of NSCLC patients receiving neoadjuvant immunotherapy.

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Data availability

The datasets generated or analyzed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and TCGA database (https://portal.gdc.cancer.gov/).

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Funding

This work was supported by the National Key R&D Program of China (2021YFC2500900), National Natural Science Foundation of China (82273129), Medical and Health Science-Technology Innovation Project of the Chinese Academy of Medical Sciences (2021-I2M-1-015), Central Health Research Key Projects (2022ZD17), and Research Project of the Institute (LC2019L01).

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Authors and Affiliations

  1. Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Yang Liu, Guangyu Bai, Qilin Huai, Yuan Li, Xiaowei Chen, Bolun Zhou & Shugeng Gao

  2. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

    Fenglong Bie

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  1. Yang Liu
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Contributions

LY (Liu Yang) analyzed the public data curation and was a major contributor in writing the manuscript. BFL collected the genomic data and performed the initial analysis of the data. BGY participated in coming up with the idea regarding the neoadjuvant immunotherapy and performed book retrieval for group discussion. HQL performed the initial review of the manuscript. LY (Li Yuan) plotted the figures and wrote the figure legends. CXW performed data interpretation and provided the methodological supportation. ZBL provided the methodological supportation and participated in writing the original draft. GSG was the corresponding author of the manuscript and provided funding acquisition. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shugeng Gao.

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Liu, Y., Bie, F., Bai, G. et al. Prognostic model based on B cell marker genes for NSCLC patients under neoadjuvant immunotherapy by integrated analysis of single-cell and bulk RNA-sequencing data. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03428-1

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