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Single-cell RNA-Seq and bulk RNA-Seq reveal reliable diagnostic and prognostic biomarkers for CRC

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Abstract

Purpose

The potential role of epithelium-specific genes through the adenoma-carcinoma sequence in the development of colorectal cancer (CRC) remains unknown. Therefore, we integrated single-cell RNA sequencing and bulk RNA sequencing data to select diagnosis and prognosis biomarkers for CRC.

Methods

The CRC scRNA-seq dataset was used to describe the cellular landscape of normal intestinal mucosa, adenoma and CRC and to further select epithelium-specific clusters. Differentially expressed genes (DEGs) of epithelium-specific clusters were identified between intestinal lesion and normal mucosa in the scRNA-seq data throughout the adenoma-carcinoma sequence. Diagnostic biomarkers and prognostic biomarker (the risk score) for CRC were selected in the bulk RNA-seq dataset based on DEGs shared by the adenoma epithelium-specific cluster and the CRC epithelium-specific cluster (shared-DEGs).

Results

Among the 1063 shared-DEGs, we selected 38 gene expression biomarkers and 3 methylation biomarkers that had promising diagnostic power in plasma. Multivariate Cox regression identified  174 shared-DEGs as prognostic genes for CRC. We combined 1000 times LASSO-Cox regression and two-way stepwise regression to select 10 prognostic shared-DEGs to construct the risk score in the CRC meta-dataset. In the external validation dataset, the 1- and 5-year AUCs of the risk score were higher than those of stage, the pyroptosis-related genes (PRG) score and the cuproptosis-related genes (CRG) score. In addition, the risk score was closely associated with the immune infiltration of CRC.

Conclusion

The combined analysis of the scRNA-seq dataset and the bulk RNA-seq dataset in this study provides reliable biomarkers for the diagnosis and prognosis of CRC.

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Data availability

Data for this study can be found in The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) and the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.

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Acknowledgements

We are indebted to all the patients who participated in studies of TCGA and GEO databases.

Funding

This study was supported by the Science and Technology Development Foundation of Shenzhen (Grant number: JCYJ20190808111817192, JCYJ20210324093807020) and the Scientific Research Initiation foundation for young teachers of Shenzhen University (Grant number: 2019123, QNJS0160).

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  1. Xing Zhang and Longkun Yang contributed equally to this article.

Authors and Affiliations

  1. Department of Epidemiology, The School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian, People’s Republic of China

    Xing Zhang, Longkun Yang, Ying Deng, Zhicong Huang & Baochang He

  2. Department of Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen University Medical School, Shenzhen, 518061, Guangdong Province, People’s Republic of China

    Hao Huang & Fulan Hu

  3. Department of Epidemiology and Health Statistics, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, People’s Republic of China

    Yuying Wu

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  1. Xing Zhang
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Contributions

Data collection and filtering: XZ, YW, LY; data analysis and figures preparation: XZ; collation of results: HH, LY; article writing: XZ; review and modify article format: XZ, YD; conceived and designed this study: BH, FH. All the authors read and approved the final manuscript.

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Correspondence to Baochang He or Fulan Hu.

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Zhang, X., Yang, L., Deng, Y. et al. Single-cell RNA-Seq and bulk RNA-Seq reveal reliable diagnostic and prognostic biomarkers for CRC. J Cancer Res Clin Oncol 149, 9805–9821 (2023). https://doi.org/10.1007/s00432-023-04882-0

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