# A preliminary study on the prognostic significance of cysteine-rich EGF ligand domain 2 protein (CRELD2) in patients with triple negative breast cancer

**Authors:** Mehmet Zahid Kocak, Murat Araz, Siddika Findik, Aykut Demirkiran, Mustafa Korkmaz, Melek Karakurt Eryilmaz, Mehmet Artac

PMC · DOI: 10.17305/bb.2024.11865 · Biomolecules and Biomedicine · 2025-01-24

## TL;DR

This study explores whether CRELD2 protein levels can predict survival outcomes in patients with triple-negative breast cancer.

## Contribution

This is the first clinical study to evaluate CRELD2 as a prognostic marker in triple-negative breast cancer.

## Key findings

- CRELD2-negative patients had better overall survival in metastatic triple-negative breast cancer.
- CRELD2 status was a significant risk factor for progression-free and overall survival in metastatic cases.
- No significant survival difference was observed in non-metastatic patients based on CRELD2 status.

## Abstract

The cysteine-rich epidermal growth factor ligand domain 2 protein (CRELD2) is associated with pathways that regulate epithelial-to-mesenchymal transition, a critical process driving cancer metastasis. This study aimed to determine the prognostic value of CRELD2 status on survival outcomes in triple-negative breast cancer (TNBC). Seventy patients were included in the study. Thirty-four patients were metastatic, and 36 patients were non-metastatic. CRELD2 protein expression in tumor tissue was determined by immunohistochemical staining (IHC). The patients were divided into two groups: CRELD2 positive and negative groups. Clinicopathological features and survival outcomes were compared between the groups. In the survival analysis of the non-metastatic patient group, five-year overall survival (OS) rate was 91.7% in the CRELD2-positive patient group and 91% in the negative group (P ═ 0.91). Median progression free survival (PFS) was 9.4 (95% confidence interval [CI]: 6.4–12.4) months in the CRELD2-positive group and 11.9 (95% CI: 8.2–18.6) months in the CRELD2-negative group (P ═ 0.04). The median OS was 17.2 (95% CI: 13.7–22.3) months in the CRELD2-positive group and 24.7 (95% CI: 21.8–29.6) months in the CRELD2-negative group (P ═ 0.02). In multivariate analysis, CRELD2 status (negative vs positive) (hazard ratio [HR]: 0.50, 95% CI: 0.38–0.96, P ═ 0.02) was determined to be a risk factor for OS and CRELD2 status (negative vs positive) (HR: 0.82, 95% CI: 0.33–0.96, P ═ 0.01) was defined as a risk factor for PFS in patients with metastatic TNBC. This is the first clinical study to determine the effect of CRELD2 on survival and as a prognostic marker in patients with triple metastatic breast cancer. These results need to be validated prospectively with a large sample size.

## Linked entities

- **Proteins:** CRELD2 (CRELD disulfide isomerase 2)
- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** CRELD2 (CRELD disulfide isomerase 2) [NCBI Gene 79174]
- **Diseases:** cancer metastasis (MESH:D009369), breast cancer (MESH:D001943), TNBC (MESH:D064726)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12097403/full.md

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Source: https://tomesphere.com/paper/PMC12097403