CRELD2 as a Prognostic Marker in Triple-Negative Breast Cancer

CRELD2 emerges as a potential prognostic marker for one of the most aggressive breast cancer subtypes

A recent study from Necmettin Erbakan University has identified a protein called CRELD2 as a possible biomarker for predicting survival in patients with triple-negative breast cancer (TNBC)—one of the most aggressive and difficult-to-treat forms of breast cancer.

Triple-negative breast cancer accounts for 10% to 20% of all breast cancers and tends to affect younger women more often. Unlike other breast cancer types, TNBC lacks estrogen receptors, progesterone receptors, and HER2 (human epidermal growth factor receptor 2). Because of this, many common targeted treatments are not effective, leaving chemotherapy as the main option. TNBC is associated with faster disease progression, a higher risk of recurrence, and lower five-year survival rates compared to other subtypes.

The new study, published in Biomolecules and Biomedicine, is the first clinical investigation of CRELD2 in human TNBC patients. The researchers found that higher levels of CRELD2 were associated with poorer survival outcomes, especially in patients whose cancer had spread to other parts of the body.

What is CRELD2 and Why is it Important?

CRELD2 (Cysteine-Rich Epidermal Growth Factor-Like Domain 2) is a stress-related protein that helps cells adapt to challenging conditions, such as low oxygen or nutrient levels—features common in aggressive tumors. Laboratory studies have suggested that CRELD2 may promote cancer cell movement and tumor growth by affecting the tumor environment and supporting the spread of cancer cells.

Although earlier research linked CRELD2 to tumor development in experimental models, its role in human cancer remained unclear. This study is the first to explore its relevance in real-world clinical settings.

Study Highlights:

Researchers analyzed tumor samples from 70 patients with TNBC, divided into those with and without metastasis. They used immunohistochemistry to measure CRELD2 levels and compared outcomes.

• In non-metastatic cases, CRELD2 levels had little impact on overall survival, but patients with higher expression saw slightly faster disease progression.
  
• In metastatic TNBC, patients with high CRELD2 expression had a median survival of 17.2 months, compared to 24.7 months for those with low levels.
  
• The amount of CRELD2 present was also linked to survival: those with more than 50% expression had the shortest survival times.
  

Multivariate analysis confirmed that CRELD2 was an independent risk factor for shorter survival in metastatic cases.

Implications and Next Steps

These findings suggest that CRELD2 could help doctors identify high-risk patients and guide treatment decisions in TNBC. As a prognostic marker, CRELD2 may also serve as a potential target for future therapies aimed at slowing disease progression.

However, the study has some limitations. It involved a relatively small number of patients and was based on retrospective data. More research is needed to understand how CRELD2 influences tumor behavior and to test its potential in larger, prospective clinical studies.

Conclusion

While current treatment options for triple-negative breast cancer remain limited, identifying proteins like CRELD2 could be a step toward more personalized care. Further research may reveal new ways to target this protein and improve outcomes for patients facing this aggressive form of cancer.

More information:

Mehmet Zahid Kocak et al, A preliminary study on the prognostic significance of cysteine-rich EGF ligand domain 2 protein (CRELD2) in patients with triple-negative breast cancer. Biomol Biomed [Internet]. 2025 Jan. 24 [cited 2025 Apr. 7];

Available from: https://doi.org/10.17305/bb.2024.11865

Journal information: Biomolecules and Biomedicine

Provided by: Association of Basic Medical Sciences of FBIH

Provided by Association of Basic Medical Sciences of FBIH