Role of CNK1, Ephrin B1, GPR19 and SMURF1 in breast cancer early diagnosis, metastasis and drug resistance

Background: The extracellular signal-regulated kinase (ERK) pathway is a key signaling pathway involved in the regulation of normal cell proliferation, survival and differentiation. However, aberrant regulations of the ERK pathway contribute to cancer and other human diseases. Objective: This study was designed to investigate the role of some ERK pathway effectors such as the connector enhancer of kinase suppressor of Ras1 (CNK1), Ephrin B1, G protein-coupled receptor 19 (GPR19) and SMAD ubiquitination regulatory factor 1 (SMURF1) in breast cancer (BC) diagnosis and metastasis risk prediction. Methods: The study involved 50 (ERPRHer2=6, ERPRHer2=11, ERPRHER2=8, ERPRHer2=25) newly diagnosed BC patients, 15 chemotherapy resistant BC patients, 15 benign breast tumor patients and 10 controls. All total 65 BC patients (including the chemotherapy resistant group) were subdivided into two groups: metastatic BC (17 patients), and nonmetastatic BC group (48 patients). CNK1, Ephrin B1, GPR19 and SMURF1 serum levels were analyzed using ELISA. Results: The study revealed significantly higher serum levels of CNK1, Ephrin B1, GPR19 and SMURF1 in all malignant groups (ERPRHer2, ERPRHer2, ERPRHER2, ERPRHer2), as well as a significant elevation in the chemotherapy resistant BC group as compared to non-resistant group (P < 0.001). They also revealed excellent value for de novo BC diagnosis and metastasis prediction. Conclusion: CNK1, Ephrin B1, GPR19 and SMURF1 may be considered as novel biomarkers for BC diagnosis and prediction of metastasis risk.