# Identification of STEAP4, EPC1, and CLEC1B as non-invasive candidate biomarkers for hepatocellular carcinoma using integrated bioinformatics analysis

**Authors:** Soheyla Khojand, Neda Zahmatkesh, Arezoo Hassani, Zahra Damerchiloo, Zahra Nikoo, Roozbeh Heidarzadehpilehrood

PMC · DOI: 10.1016/j.btre.2026.e00953 · 2026-02-26

## TL;DR

This study identifies STEAP4, EPC1, and CLEC1B as potential non-invasive biomarkers for diagnosing and predicting outcomes in hepatocellular carcinoma.

## Contribution

The study identifies novel non-invasive biomarkers for hepatocellular carcinoma by integrating PBMC and tumor transcriptomic data.

## Key findings

- STEAP4, EPC1, and CLEC1B are associated with poorer survival in HCC patients.
- Immune-related pathways are dysregulated in PBMCs, while metabolic pathways are altered in tumor tissues.
- Shared DEGs between PBMCs and tumor tissues suggest potential for non-invasive biomarkers.

## Abstract

•Cytokine-related pathways dysregulated in hepatocellular carcinoma (HCC)•STEAP4, EPC1, CLEC1B, and LCN2 were identified as the shared non-invasive biomarkers.•
Targeted miRNAs were identified, including miR-107, miR-326, GAS5, MALAT1, PRLP0P6, and SNHG1.
•Protein-protein networks were constructed between mRNAs and miRNAs in HCC.

Cytokine-related pathways dysregulated in hepatocellular carcinoma (HCC)

STEAP4, EPC1, CLEC1B, and LCN2 were identified as the shared non-invasive biomarkers.

Targeted miRNAs were identified, including miR-107, miR-326, GAS5, MALAT1, PRLP0P6, and SNHG1.

Protein-protein networks were constructed between mRNAs and miRNAs in HCC.

The high global mortality of hepatocellular carcinoma (HCC) underscores the need for reliable non-invasive diagnostic biomarkers. In this study, transcriptomic analyses were performed on peripheral blood mononuclear cell (PBMC) and tumor datasets from HCC patients to identify differentially expressed genes (DEGs) using an adjusted p-value 〈 0.01 and |log2FC| 〉 1. Functional enrichment analyses revealed predominant immune-related pathways in PBMCs and metabolic pathway dysregulation in tumor tissues. Integration of PBMC and tumor profiles identified STEAP4, EPC1, CLEC1B, and LCN2 as shared DEGs. Survival analyses indicated that elevated expression of STEAP4, EPC1, and CLEC1B was associated with poorer overall survival in HCC patients. Collectively, these findings highlight consistent transcriptional alterations in PBMCs and tumor tissues and suggest that STEAP4, EPC1, and CLEC1B may serve as potential non-invasive biomarkers with diagnostic and prognostic relevance in HCC.

## Linked entities

- **Genes:** STEAP4 (STEAP4 metalloreductase) [NCBI Gene 79689], EPC1 (enhancer of polycomb 1) [NCBI Gene 80314], CLEC1B (C-type lectin domain family 1 member B) [NCBI Gene 51266], LCN2 (lipocalin 2) [NCBI Gene 3934], MIR107 (microRNA 107) [NCBI Gene 406901], MIR326 (microRNA 326) [NCBI Gene 442900], GAS5 (growth arrest specific 5) [NCBI Gene 60674], MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938], SNHG1 (small nucleolar RNA host gene 1) [NCBI Gene 23642]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** EPC1 (enhancer of polycomb 1) [NCBI Gene 80314] {aka Epl1}, CLEC1B (C-type lectin domain family 1 member B) [NCBI Gene 51266] {aka 1810061I13Rik, CLEC2, PRO1384, QDED721}, STEAP4 (STEAP4 metalloreductase) [NCBI Gene 79689] {aka STAMP2, SchLAH, TIARP, TNFAIP9}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}
- **Diseases:** HCC (MESH:D006528), tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13019070/full.md

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Source: https://tomesphere.com/paper/PMC13019070