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Article Open Access

CANT1 as a novel prognostic biomarker in triple‑negative breast cancer

  • Authors:
    • Doğan Bayram
    • Aysel Çolak
    • Şefi̇ka Karabulut
    • Sema Nur Özsan Çelebi̇
    • Emre Hafizoğlu
    • Duri̇ye Özer Türkay
    • Öznur Bal
    • Efnan Algin
    • Şebnem Yücel
    • Mehmet Ali̇ Nahi̇t Şendur
    • Burak Ci̇velek
    • Gökhan Uçar

  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Ankara City Hospital, Ankara 06800, Turkey, Department of Pathology, Ankara City Hospital, Ankara 06800, Turkey, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Gazi University, Ankara 06330, Turkey, Department of Medical Oncology, Afyonkarahisar State Hospital, Afyonkarahisar 03110, Turkey
    Copyright: © Bayram et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 166
    |
    Published online on: March 9, 2026
       https://doi.org/10.3892/ol.2026.15519
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Abstract

Triple‑negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, with limited targeted treatment options and poor clinical outcomes. Calcium‑activated nucleotidase 1 (CANT1), a calcium dependent enzyme involved in nucleotide metabolism and glycoprotein processing, has attracted limited attention in oncology and its clinical relevance in breast cancer remains unknown. The present study hypothesized that CANT1 expression may carry prognostic information in TNBC and evaluated its association with clinicopathologicalal features and survival. In the present retrospective study, 59 non‑metastatic patients with TNBC who underwent curative surgery were included. CANT1 expression was assessed using immunohistochemistry and semiquantitatively scored using an H‑score ranging from 1‑300. Patients were categorized into three groups according to H‑score (H1, 1‑100; H2, 101‑200; H3, 201‑300). Associations between CANT1 expression and clinicopathologicalal variables were analyzed using the χ2 or Fisher's exact test and survival outcomes were evaluated using the Kaplan‑Meier method, log‑rank test and Cox proportional hazards model. CANT1 expression was successfully evaluated in all tumors: 15 patients (25.4%) were classified as H1, 29 (49.2%) as H2 and 15 (25.4%) as H3. The median overall survival (OS) for the entire cohort was 40.2 months, with a median follow‑up of 48.4 months. Median OS by expression group was 29.2 months in H1, 36.7 months in H2 and not reached in H3 (log‑rank P=0.033). In the multivariable analysis, high CANT1 expression (H3 vs. H1) remained independently associated with improved OS (P=0.048; hazard ratio=0.149; 95% CI, 0.031‑0.715). To the best of our knowledge, the present study is the first to investigate CANT1 expression in TNBC. High CANT1 expression was significantly assocaited with improved OS, suggesting that CANT1 may serve as a novel prognostic biomarker in TNBC. Further multicenter and mechanistic studies are warranted to clarify its biological role and prognostic utility.
View Figures

Figure 1

Representative immunohistochemical staining of CANT1 in triple-negative breast cancer showing 0 (negative), 1+, 2+ and 3+ cytoplasmic staining intensities. (A) Strong (3+) cytoplasmic and perinuclear granular positivity in 100% of invasive tumor cells. (B) Strong (3+) staining in ~80% of tumor cells. (C) Strong (3+) staining in ~70% of tumor cells. (D) Strong (3+) staining in ~70% of tumor cells. (E) Strong (3+) staining in ~60% of tumor cells. (F) Moderate (2+) cytoplasmic staining in ~60% of tumor cells. (G) CANT1 staining in peritumoral lymphocytes showing focal (~5%) positivity. (H) CANT1 staining in peritumoral lymphocytes showing diffuse (~80%) positivity. (I) Moderate (2+) cytoplasmic staining in ~40% of tumor cells. (J) Weak (1+) cytoplasmic staining in ~20% of tumor cells. (K) Weak (1+) cytoplasmic staining in ~40% of tumor cells. (L) Absence of CANT1 staining in invasive tumor cells (negative, 0). (M) Weak (1+) cytoplasmic staining in ~50% of tumor cells. (N) Peritumoral lymphocytes showing focal (~20%) positivity. (O) Peritumoral lymphocytes showing absence of staining.

Figure 2

Sankey diagram of CANT1 expression patterns and H-score groups illustrating the relationship between semi-quantitative CANT1 staining patterns (left), calculated H-score values (middle) and predefined H-score groups (right) in 59 patients with triple-negative breast cancer. The left column represents combinations of staining intensity (1+, 2+ or 3+) and the percentage of positive tumor cells, the middle column shows the resulting H-score for each pattern (range, 20–300) and the right column shows the three H-score categories: Group 1 (H1, 1–100; n=15), group 2 (H2, 101–200; n=29) and group 3 (H3, 201–300; n=15). The width of each band is proportional to the number of patients contributing to that transition. CANT1, calcium-activated nucleotidase 1.

Figure 3

Kaplan-Meier overall survival curves according to CANT1 H-score categories (H1, 1–100; H2, 101–200; H3, 201–300). Vertical tick marks indicate censored observations. CANT1, calcium-activated nucleotidase 1.

Figure 4

Correlation between CANT1 H-score and Ki-67 proliferation index. Scatter plot illustrating the relationship between CANT1 H-score and Ki-67 index in 56 patients with triple-negative breast cancer. Data points are color-coded according to CANT1 H-score categories (H1, 1–100; H2, 101–200; H3, 201–300). The solid line represents the linear regression fit, demonstrating a weak negative correlation (Pearson r=−0.189). CANT1, calcium-activated nucleotidase 1.
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Copy and paste a formatted citation
Spandidos Publications style
Bayram D, Çolak A, Karabulut Ş, Özsan Çelebi̇ SN, Hafizoğlu E, Türkay DÖ, Bal Ö, Algin E, Yücel Ş, Şendur MA, Şendur MA, et al: CANT1 as a novel prognostic biomarker in triple‑negative breast cancer. Oncol Lett 31: 166, 2026.
APA
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S.N., Hafizoğlu, E., Türkay, D.Ö. ... Uçar, G. (2026). CANT1 as a novel prognostic biomarker in triple‑negative breast cancer. Oncology Letters, 31, 166. https://doi.org/10.3892/ol.2026.15519
MLA
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S. N., Hafizoğlu, E., Türkay, D. Ö., Bal, Ö., Algin, E., Yücel, Ş., Şendur, M. A., Ci̇velek, B., Uçar, G."CANT1 as a novel prognostic biomarker in triple‑negative breast cancer". Oncology Letters 31.5 (2026): 166.
Chicago
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S. N., Hafizoğlu, E., Türkay, D. Ö., Bal, Ö., Algin, E., Yücel, Ş., Şendur, M. A., Ci̇velek, B., Uçar, G."CANT1 as a novel prognostic biomarker in triple‑negative breast cancer". Oncology Letters 31, no. 5 (2026): 166. https://doi.org/10.3892/ol.2026.15519
Copy and paste a formatted citation
x
Spandidos Publications style
Bayram D, Çolak A, Karabulut Ş, Özsan Çelebi̇ SN, Hafizoğlu E, Türkay DÖ, Bal Ö, Algin E, Yücel Ş, Şendur MA, Şendur MA, et al: CANT1 as a novel prognostic biomarker in triple‑negative breast cancer. Oncol Lett 31: 166, 2026.
APA
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S.N., Hafizoğlu, E., Türkay, D.Ö. ... Uçar, G. (2026). CANT1 as a novel prognostic biomarker in triple‑negative breast cancer. Oncology Letters, 31, 166. https://doi.org/10.3892/ol.2026.15519
MLA
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S. N., Hafizoğlu, E., Türkay, D. Ö., Bal, Ö., Algin, E., Yücel, Ş., Şendur, M. A., Ci̇velek, B., Uçar, G."CANT1 as a novel prognostic biomarker in triple‑negative breast cancer". Oncology Letters 31.5 (2026): 166.
Chicago
Bayram, D., Çolak, A., Karabulut, Ş., Özsan Çelebi̇, S. N., Hafizoğlu, E., Türkay, D. Ö., Bal, Ö., Algin, E., Yücel, Ş., Şendur, M. A., Ci̇velek, B., Uçar, G."CANT1 as a novel prognostic biomarker in triple‑negative breast cancer". Oncology Letters 31, no. 5 (2026): 166. https://doi.org/10.3892/ol.2026.15519
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