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Identification of a novel prognostic signature composed of 3 cuproptosis-related transcription factors in colon adenocarcinoma

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Abstract

Background

Since the mechanism of cuproptosis was recently revealed, many molecules related to this pathway have been widely concerned and exploited to have prognostic potential. However, it is still unknown whether the transcription factors related to cuproptosis could be competent as tumor biomarkers of colon adenocarcinoma (COAD).

Objective

To analyze the prognostic potential of cuproptosis-related transcription factors in COAD, and validate the representative molecule.

Methods

Transcriptome data and patients’ clinical parameters were obtained from the TCGA and GEO database. 19 cuproptosis genes were identified through literature consulting. Cuproptosis-related transcription factors were screened by COX regression analyses. Multivariate Cox regression was applied to construct the signature. Prognostic effects were evaluated by Kaplan Meier survival analyses and ROC analyses. KEGG, GO, and ssGSEA analyses were performed for function prediction. 48 COAD tissues were collected for immunohistochemistry stain to observe the expression level and prognostic value of E2F3.

qRT-PCR was performed to detect mRNA expression levels, while cell viability assay was applied to detect the response of COAD cells to elesclomol treatment.

Results

A novel signature based on 3 prognostic transcription factors related to cuproptosis was successfully established and verified. Patients in the low-risk group tended to have better overall survival and lower immune phenotype scores than those in the high-risk group. Meanwhile, we also constructed a nomogram based on this signature and predict 10 candidate compounds targeting this signature. As an essential member of this signature, E2F3 was confirmed to be overexpressed in COAD tissues and was associated with poor prognosis of COAD patients. Importantly, CuCl2 and cuproptosis inducer elesclomol treatment could increase the expression of E2F3 in COAD cell while the overexpression of E2F3 significantly enhanced the resistance of COAD cells to elesclomol treatment.

Conclusion

Our research has identified a new prognostic biomarker and provides some innovative insights into the diagnosis and therapy of patients with COAD.

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Data availability

All data supporting our outcomes will be obtained from the corresponding authors upon appropriate requests.

Abbreviations

COAD:

Colon adenocarcinoma

CTFPS:

CTF-based prognostic signature

IC:

Immune checkpoint

IHC:

Immunohistochemistry

IRS:

Immunoreactive score

PFS:

Progression-free survival

CTF:

Cuproptosis-related transcription factor

DFS:

Disease-free survival

ICB:

Immune checkpoint blocker

IPS:

Immunophenotypic score

OS:

Over survival

TF:

Transcription factor

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Acknowledgements

We thank all developers of the databases and R software packages involved in the present research.

Funding

This research was supported by the Special Funds for Science Development of the Clinical Teaching Hospitals of Jiangsu Vocational College of Medicine (20229121).

Author information

Authors and Affiliations

  1. The Graduate School, Dalian Medical University, Dalian, Liaoning, China

    Lei Zhou & Liming Tang

  2. Department of General Surgery, Yancheng Third People’s Hospital, The Clinical Teaching Hospital of Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, China

    Lei Zhou

  3. Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu, China

    Yixin Xu & Tao Jiang

  4. Department of General Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, No. 68 Gehu Middle Road, Changzhou, 213164, Jiangsu, China

    Liming Tang

  5. School of Management, Xuzhou Medical University, Xuzhou, Jiangsu, China

    Yuwan Zhang

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  1. Lei Zhou
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  4. Tao Jiang
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Contributions

LMT, and TJ conceived and designed this study. YWZ and YYX downloaded and sorted out the relevant data from the TCGA database. LZ and TJ screened the CTFs, constructed and validated the CTFPS, predicted the function, established the nomogram, and predicted candidate compounds. LZ, YWZ, and YXX conducted IHC, evaluated the IRS, and performed the qRT-PCR and cell viability assays. LZ, LMT and TJ designed the primers, analyzed the data, plotted the figures, drew the table, and wrote the manuscripts. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Tao Jiang or Liming Tang.

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Zhou, L., Zhang, Y., Xu, Y. et al. Identification of a novel prognostic signature composed of 3 cuproptosis-related transcription factors in colon adenocarcinoma. Genes Genom 45, 1047–1061 (2023). https://doi.org/10.1007/s13258-023-01406-5

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  • DOI: https://doi.org/10.1007/s13258-023-01406-5

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