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Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma

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Abstract

Background

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential.

Method

We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD.

Results

We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways.

Conclusions

Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.

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Data availability

The experimental data that support the findings of this study are available in Figshare with the identifier https://doi.org/10.6084/m9.figshare.25027181.v1.

Abbreviations

NSCLC:

Non-small cell lung cancer

LUAD:

Lung Adenocarcinoma

GEO:

Gene Expression Omnibus Database

TCGA:

The Cancer Genome Atlas

KEGG:

Kyoto encyclopedia of genes and genomes

ScRNA-seq:

Single-cell RNA sequencing

TME:

Tumor microenvironment

CNV:

Copy number variations

EMT:

Epithelial-mesenchymal transition

PDX:

patient-derived xenografts

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Acknowledgements

Thanks to the patients who provided clinical data for this medical study.

Funding

This research was supported by the Clinical Research Incubation Project of West China Hospital of Sichuan University (2018HXFH012) and the National Natural Science Foundation of China (82173251).

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Author notes

  1. Shengqiang Mao, Yilong Wang and Ningning Chao have contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

    Shengqiang Mao, Yilong Wang, Ningning Chao, Lingyan Zeng & Li Zhang

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  1. Shengqiang Mao
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Contributions

LZ conceived the project and designed the experiments. SQM, YLW and NNC were involved in the analysis of the experiments and wrote the paper. SQM performed the bioinformatic analysis. YLW, NNC and LYZ contributed to the experiments and analyzed the data. All the authors discussed the results and reviewed the manuscript.

Corresponding author

Correspondence to Li Zhang.

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Ethics approval and consent to participate

This study was approved by the Research Ethics Committee of West China Hospital, Sichuan University. Ethical approval for this study was provided by the Ethics Committee on Biomedical research, West China Hospital of Sichuan University on 18/12/2020.

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Mao, S., Wang, Y., Chao, N. et al. Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00948-4

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