Dataset Information

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer.

ABSTRACT: 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.

SUBMITTER: Aroca-Siendones MI

PROVIDER: S-EPMC8391187 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer.

Aroca-Siendones María I MI Moreno-SanJuan Sara S Puentes-Pardo Jose D JD Verbeni Michela M Arnedo Javier J Escudero-Feliu Julia J García-Costela María M García-Robles Adelina A Carazo Ángel Á León Josefa J

Biomedicines 20210806 8

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 an ...[more]

PMID: 34440171

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Project description:BackgroundProstate cancer (PC) is one of the most common malignancies in males. Extensive and complex connections between circadian rhythm and cancer were found. Nonetheless, in PC, the potential role of the core components of the mammalian circadian clock (CCMCCs) in prognosis prediction has not been fully clarified.MethodsWe firstly collected 605 patients with PC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis was carried out for each CCMCC. Then, we investigated the prognostic ability of CCMCCs by Cox regression analysis. Independent prognostic signatures were extracted for the establishment of the circadian clock-based risk score model. We explored the predictive performance of the risk score model in the TCGA training cohort and the independent GEO dataset. Finally, the relationships between risk score and clinicopathological parameters, biological processes, and signaling pathways were evaluated.ResultsThe expression levels of CCMCCs were widely correlated with age, tumor status, lymph node status, disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Nine circadian clock genes, including CSNK1D, BTRC, CLOCK, CSNK1E, FBXL3, PRKAA2, DBP, NR1D2, and RORB, were identified as vital prognostic factors in PC and were used to construct the circadian clock-based risk score model. For DFS, the area under the 3-year or 5-year receiver operating characteristic curves ranged from 0.728 to 0.821, suggesting better predictive performance. When compared with T3-4N1 stage, PC patients at T2N0 stage might be benefited more from the circadian clock-based risk score model. Furthermore, a high circadian clock-based risk score indicated shorter DFS (p < 0.0001), early progression (p < 0.0001), and higher 5-year death rate (p = 0.007) in PC. The risk score was related to tumor status (p < 0.001), lymph node status (p < 0.001), and ribosome-related biogenesis and pathways.ConclusionsThe vital roles of circadian clock genes in clinical outcomes were fully depicted. The circadian clock-based risk score model could reflect and predict the prognosis of patients with PC.

Dataset Information

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer.

Publications

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer.

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