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Comprehensive analysis of novel cancer prediction genes and tumor microenvironment infiltration in colon cancer

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Abstract

Background

Colon cancer with high incidence and mortality is a severe public health problem. As an emerging therapy, immunotherapy has played an active clinical role in tumor treatment, but only a small number of patients respond.

Methods

By univariate Cox regression analysis of 165 novel cancer prediction genes (NCPGs), 29 NCPGs related to prognosis were screened. Based on these 29 NCPGs and 336 differentially expressed genes, we constructed two colon cancer subgroups and three gene clusters and analyzed prognosis, activation pathways, and immune infiltration characteristics under various modification patterns. Then each patient was scored and divided into high or low NCPG_score groups. A comprehensive evaluation between NCPG_score and clinical characteristics, tumor microenvironment (TME), tumor somatic mutations, and the potential for immunotherapy was conducted.

Results

Patients with high NCPG_score were characterized by high tumor mutation burden and high microsatellite instability and were more suitable for immunotherapy.

Conclusions

This study screened 29 NCPGs as independent prognostic markers in colon cancer patients, demonstrating their TME, clinicopathological features, and potential roles in immunotherapy, helping to assess prognosis and guiding more personalized immunotherapy.

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Availability of data and materials

The data sets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/), accession numbers TCGA-COAD, COAD-FPKM; GEO repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39582).

Abbreviations

CNV:

Copy number variation

DEGs:

Differentially expressed genes

FDA:

Food and Drug Administration

ICB:

Immune-checkpoint blocker

MSI:

Microsatellite instability

MSI-H:

High microsatellite instability

MDSCs:

Myeloid-derived suppressor cells

NCPGs:

Novel cancer prediction genes

PCA:

Principal component analysis

ssGSEA:

Single sample gene set enrichment analysis

TCGA:

The cancer genome Atlas

TGF-beta:

Transforming growth factor beta

TMB:

Tumor mutation burden

TME:

Tumor microenvironment

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Acknowledgements

The authors gratefully acknowledge TCGA and GEO databases providing their platforms for offering convenient access to datasets and the contributors for uploading their meaningful datasets.

Funding

This study was funded by the National Science Foundation of China (No. 81903539).

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Authors and Affiliations

  1. Department of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China

    Shixin Wang & Sujie Zhu

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  1. Shixin Wang
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Contributions

SZ was responsible for the concept and design of the original study and performed a systematic search in the literature of original articles. SW performed the data analysis and manuscript preparation, SZ was responsible for the critical review of the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Sujie Zhu.

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Wang, S., Zhu, S. Comprehensive analysis of novel cancer prediction genes and tumor microenvironment infiltration in colon cancer. Clin Transl Oncol 25, 2545–2558 (2023). https://doi.org/10.1007/s12094-023-03145-1

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