Differential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns

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dc.contributor.authorCielo Garcia Montero
dc.contributor.authorOscar Fraile Martinez
dc.contributor.authorAna M. Minaya Bravo
dc.contributor.authorDiego Liviu Boaru
dc.contributor.authorDiego De Leon Oliva
dc.contributor.authorPatricia De Castro Martinez
dc.contributor.authorMajd N. Michael Alhaddadin
dc.contributor.authorSilvestra Barrena Blázquez
dc.contributor.authorLaura Lopez Gonzalez
dc.contributor.authorLuis G. Guijarro
dc.contributor.authorNatalio Garcia Honduvilla
dc.contributor.authorVíctor Roberto Baena Romero
dc.contributor.authorCarlos Daniel Padilla Ansala
dc.contributor.authorMar Royuela
dc.contributor.authorMaría Del Val Toledo Lobo
dc.contributor.authorLeonel Pekarek
dc.contributor.authorRoberto Fernández Baillo Gallego de la Sacristana
dc.contributor.authorMauricio Hernández Fernández
dc.contributor.authorMontserrat Chao Crecente
dc.contributor.authorMelchor Alvarez-Mon
dc.contributor.authorRaul Diaz-Pedrero
dc.contributor.authorMiguel A. Ortega
dc.contributor.authorMiguel A. Saez
dc.contributor.departmentBiología Celular e Histología
dc.date.accessioned2025-11-11T08:44:10Z
dc.date.available2025-11-11T08:44:10Z
dc.date.issued2025
dc.description.abstractColorectal cancer (CRC) is a leading cause of cancer-related mortality, with an incidence projected to rise significantly worldwide. While TNM staging remains the cornerstone of prognosis and treatment decisions, additional biomarkers are needed to enhance predictive accuracy and therapeutic targeting. Ferroptosis, an iron-dependent cell death pathway, has emerged as a key regulator of CRC progression and therapy resistance. Circadian rhythms, KLOTHO, and tumor suppressors, such as p53, CDKN1A (p21), and Rb, also play crucial roles in CRC biology. Integrating TNM staging with molecular markers and patient-specific variables offers a more precise, personalized approach to CRC management. In the present work, we analyze the histopathological expression of KLOTHO, ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian regulators (CLOCK, BMAL1, PER1, and PER2), and classical tumor suppressors (p53, p21, and Rb) in a cohort of 63 patients diagnosed with CRC. Besides, we have considered important clinical variables, like sex, age, and anatomical location, in our statistical analysis; correlation with the protein expression of these markers was also included for each stage (T1, T2, and T3). Our study reveals that advanced CRC stages (primarily T3) exhibit increased expression of ferroptosis markers (TFRC, ALOX5, ACSL4, and GPX4) and tumor suppressors (p53, p21, and Rb), alongside reduced histopathological detection of KLOTHO and circadian markers (BMAL1, CLOCK, PER1, and PER2) compared with earlier stages. Age, but not sex, influenced the expression of several markers. Tumor location also played a role, with right-sided CRCs showing significant stage-related differences in ferroptosis, tumor suppressor, and BMAL1, whereas left-sided tumors exhibited variations primarily in circadian markers (CLOCK, PER1, and PER2). Correlation analyses across tumor stages indicate dynamic shifts, with tumor suppressors maintaining positive associations with ferroptosis markers and anti-aging/circadian markers showing stage-dependent changes. Despite the inherent limitations of our study, these findings highlight the evolving biomarker landscape in CRC progression, although further research is needed to elucidate their clinical implications.
dc.formatapplication/pdf
dc.format.extent25
dc.identifier.doihttps://doi.org/10.14670/HH-18-988
dc.identifier.eissn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/172089
dc.languageeng
dc.relationSin financiacion externa a la Universidad
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHistopathology
dc.subjectCancer progression
dc.subjectTumor staging
dc.subjectFerroptosis
dc.subjectCircadian rhythms
dc.subjectAging
dc.subjectTumor suppression
dc.subjectColorectal cancer (CRC)
dc.subject.odsNo relacionado con ningún objetivo de desarrollo sostenible
dc.titleDifferential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns
dc.typeinfo:eu-repo/semantics/article
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Histology and histopathology, Vol.40, Nº12, (2025)