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Untargeted metabolomics and lipidomics identified four subtypes of small cell lung cancer

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Abstract

Introduction

Small cell lung cancer (SCLC) is a heterogeneous malignancy with dismal prognosis. However, few studies have conducted on the metabolic heterogeneity in SCLC.

Objective

We therefore identify SCLC classifications using untargeted metabolomics and lipidomics. We also compared their survival and the immunotherapy responses.

Methods

Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC–MS/MS) analysis was performed in 191 SCLC serum samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to identify metabolic pathways. The Kaplan–Meier and log-rank test were used to analyze the survival curves. The univariate and multivariate Cox proportional hazards regression models were used to evaluate prognostic factors for OS in patients with SCLC.

Results

Distinct subtypes of SCLC were identified by consensus clustering algorithm using partioning around medoids (pam) based on untargeted metabolomics and lipidomics. Four distinct subtypes of SCLC were identified, with distinct metabolic pathways. Subgroup 2 had the longest survival whereas Subgroup 1 had the shortest. Subtype 2 benefited most from immunotherapy in OS, as in contrast to Subtype 3 with shortest survival.

Conclusion

Our study revealed the metabolic heterogeneity in SCLC and identified four subtypes with distinct metabolic features. It indicates promising therapeutic and prognostic value that may guide treatment for SCLC. The subtype-specific clinical trials may be designed and would be instructive for drug development.

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Data availability

Methods and materials are available in supplementary file.

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Funding

This study was supported jointly by Special Funds for Taishan Scholars Project (Grant No. tsqn201812149), Academic promotion program of Shandong First Medical University (2019RC004).

Author information

Author notes

  1. Chenyue Zhang and Xiaoling Shang have contributed equally to this work.

Authors and Affiliations

  1. Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Chenyue Zhang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Chenyue Zhang

  3. Shandong Cancer Hospital and Institute, Shandong University, Jinan, 250012, China

    Xiaoling Shang

  4. Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China

    Haiyong Wang

Authors
  1. Chenyue Zhang
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  2. Xiaoling Shang
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Contributions

CZ wrote the main manuscript and prepared Fig. 1. XS performed data analysis, prepared supplementary materials and revised the manuscript. HW conceived the idea and revised the manuscript. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Haiyong Wang.

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Ethical approval

This study was approved by the Ethics Committee of Shandong Cancer Hospital and Institute. All included patients in this study offered written informed consent.

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Zhang, C., Shang, X. & Wang, H. Untargeted metabolomics and lipidomics identified four subtypes of small cell lung cancer. Metabolomics 19, 3 (2023). https://doi.org/10.1007/s11306-022-01964-x

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