# Identification of unique biomarkers in colorectal cancer based on comprehensive analysis and machine learning

**Authors:** Liwei Wang, Aigang Ren, Xiaolong Cui, Yuan Shen, Qingxing Huang

PMC · DOI: 10.3389/fonc.2025.1678750 · Frontiers in Oncology · 2026-01-26

## TL;DR

This study identifies seven key genes linked to colorectal cancer that could serve as potential biomarkers for diagnosis and treatment.

## Contribution

The novel contribution is the identification of seven hub RBP genes associated with ferroptosis suppression in colorectal cancer.

## Key findings

- Fourteen ferroptosis-mitochondria-RBP-related genes were identified, including seven hub RBP genes.
- The seven hub genes showed high diagnostic accuracy with AUC values between 0.818 and 0.924.
- These genes are associated with ferroptosis suppression by regulating GSH/GSSG and Fe²⁺ levels.

## Abstract

Colorectal cancer (CRC) is a common malignant tumor with high incidence and poor prognosis. Identifying effective biomarkers is crucial for its diagnosis and treatment.

Gene expression data were obtained from TCGA-CRC and GSE39582 datasets. After preprocessing, differentially expressed genes (DEGs) were screened using the limma package. Hub genes were identified via WGCNA, miRNA-hub/TF-hub gene network construction, and LASSO, SVM-RFE, and random forest algorithms. Subtype analysis, survival analysis, external validation, qRT-PCR, Western blot, and ferroptosis-related assays were performed.

Fourteen ferroptosis-mitochondria-RBP-related genes (IMRBPs) were identified, including seven hub RBP genes (APEX1, BRCA1, DNMT1, EZH2, PTTG1, SND1, UHRF1). APEX1 was downregulated in CRC, while the other six were upregulated. The diagnostic model based on these seven genes showed high AUC values (0.818-0.924) in multiple datasets. These hub genes were associated with ferroptosis suppression by regulating GSH/GSSGand Fe²⁺ levels.

The seven hub RBP genes are potential biomarkers for CRC, providing new insights and therapeutic targets. However, functional validation and larger sample sizes are needed for clinical application.

## Linked entities

- **Genes:** APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328], BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672], DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786], EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146], PTTG1 (PTTG1 regulator of sister chromatid separation, securin) [NCBI Gene 9232], SND1 (staphylococcal nuclease and tudor domain containing 1) [NCBI Gene 27044], UHRF1 (ubiquitin like with PHD and ring finger domains 1) [NCBI Gene 29128]
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** PTTG1 (PTTG1 regulator of sister chromatid separation, securin) [NCBI Gene 9232] {aka EAP1, ECRAR, HPTTG, PTTG, TUTR1}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, SND1 (staphylococcal nuclease and tudor domain containing 1) [NCBI Gene 27044] {aka TDRD11, TSN, Tudor-SN, p100}, APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328] {aka APE, APE1, APEN, APEX, APX, HAP1}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, UHRF1 (ubiquitin like with PHD and ring finger domains 1) [NCBI Gene 29128] {aka ICBP90, Np95, RNF106, TDRD22, hNP95, hUHRF1}
- **Diseases:** CRC (MESH:D015179), malignant tumor (MESH:D009369)
- **Chemicals:** Fe2+ (-), GSH (MESH:D005978)

## Full text

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## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12883654/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12883654/full.md

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Source: https://tomesphere.com/paper/PMC12883654