Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer Aroca Siendones, María I. Moreno SanJuan, Sara Puentes Pardo, José David Verbeni, Michela Arnedo Fernández, Francisco Javier Escudero Feliú, Julia García Costela, María García Robles, Adelina Carazo Gallego, Ángel León, Josefa Colorectal cancer Core circadian clock Metachronous metastasis Local recurrence Overall survival Disease free-survival Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment. 2021-09-22T09:53:06Z 2021-09-22T09:53:06Z 2021 journal article Aroca-Siendones, M.I.; Moreno-SanJuan, S.; Puentes-Pardo, J.D.; Verbeni, M.; Arnedo, J.; Escudero-Feliu, J.; García-Costela, M.; García-Robles, A.; Carazo, Á.; León, J. Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer. Biomedicines 2021, 9, 967. https://doi.org/10.3390/ biomedicines9080967 http://hdl.handle.net/10481/70354 10.3390/biomedicines9080967 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI