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Abstract Abstract Background: Potassium channel tetramerization domain containing 12 (KCTD12) showed contradictory roles in many cancers, however, its role in breast cancer is unknown. Cripto-1 participates activates the Notch signaling pathway which was inhibited by KCTD12 in esophageal squamous cell carcinoma (ESCC). Uncoordinated 51-like kinase 2 (ULK2) with established roles in cancer was negatively regulated by KCTD12. Multidrug resistance protein 1 (MDR1) promotes resistance by an active transport efflux pump. KCTD12 downregulates the expression of drug-resistant proteins as ABCC4 and ABCG2 in ESCC patients. Purpose: We investigated the markers role in the early breast cancer. Methods: Sixty-five patient’s serum samples were compared with 10 controls and 15 benign ones. Results: Higher serum levels of KCTD12, Cripto-1, MDR1, and ULK2 in all malignant cases suggesting novel roles with better sensitivity and specificity along with CA15.3, where the resistant group was the highest suggesting value for de-novo breast cancer diagnosis. Conclusion: Positive correlations for KCTD12 with Cripto-1, MDR1, and ULK2 suggesting a new role of KCTD12. The cumulated ROC curves with CA15.3 revealed better sensitivity and specificity highlighting the add on of using more than one marker. |