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. 2025 May 8;25(7):1663-1671.
doi: 10.17305/bb.2024.11865.

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

Mehmet Zahid Kocak  1 , Murat Araz  1 , Siddika Findik  2 , Aykut Demirkiran  1 , Mustafa Korkmaz  1 , Melek Karakurt Eryilmaz  1 , Mehmet Artac  1
Affiliations

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

Mehmet Zahid Kocak et al. Biomol Biomed. .

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.

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Conflict of interest statement

Conflicts of interest: Authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Immunohistochemical staining of CRELD2 protein. (A) Negative expression of CRELD2 (no staining) (×100 magnification); (B) CRELD2 expression in 1%–10% of tumor cells (×200 magnification); (C) CRELD2 expression in 11%–50% of tumor cells (×100 magnification); (D) CRELD2 expression in >50% of tumor cells (×200 magnification). CRELD2: Cysteine-rich epidermal growth factor ligand domain 2.
Figure 2.
Figure 2.
(A and B) Kaplan Meier curves for progression free survival (mPFS) and overall survival (mOS) according to CRELD2 positive and negative groups in the metastatic triple negative breast cancer. CRELD2: Cysteine-rich epidermal growth factor ligand domain 2; CI: Confidence interval.
See this image and copyright information in PMC

References

    1. Helenius A, Marquardt T, Braakman I. The endoplasmic reticulum as a protein-folding compartment. Trends Cell Biol. 1992;2:227–31. https://doi.org/10.1016/0962-8924(92)90309-B. - PubMed
    1. Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2008;7:1013–30. https://doi.org/10.1038/nrd2755. - PubMed
    1. Okada T, Yoshida H, Akazawa R, Negıshı M, Mori K. Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J. 2002;366:585–94. https://doi.org/10.1042/bj20020391. - PMC - PubMed
    1. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107:881–91. https://doi.org/10.1016/s0092-8674(01)00611-0. - PubMed
    1. Oh-hashi K, Koga H, Ikeda S, Shimata K, Hirata Y, Kiuchi K. CRELD2 is a novel endoplasmic reticulum stress-inducible gene. Biochem Biophys Res Commun. 2009;387:504–10. https://doi.org/10.1016/j.bbrc.2009.07.047. - PubMed

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