Relevancia del gen MACC1 como biomarcador pronóstico en la progresión metastásica del cáncer colorrectal
DOI:
https://doi.org/10.62305/biosana.v6i1.913Palabras clave:
MACC1; Cáncer colorrectal; Metástasis; Biomarcadores; Pronóstico, biomarcadores; carcinoma hepatocelular; diagnóstico tempranoResumen
El cáncer colorrectal (CCR) constituye una de las principales causas de morbimortalidad a nivel mundial, y la progresión metastásica continúa siendo uno de los factores que tiene un gran impacto negativo sobre el pronóstico. En este contexto, el gen Metastasis Associated in Colon Cancer 1 (MACC1) ha surgido como un posible biomarcador de interés debido a su interacción en la activación del eje HGF/MET y de vías de señalización involucradas en proliferación, invasión y diseminación tumoral. Las limitaciones en los marcadores convencionales impulsan la evaluación del potencial clínico de MACC1 como herramienta complementaria para estratificar riesgo metastásico. El estudio a profundidad de este gen permite señalar que su sobreexpresión se asocia con menor supervivencia global, mayor tasa de recurrencia y un fenotipo tumoral más agresivo. Asimismo, se explora su valor pronóstico en etapas tempranas de la enfermedad, permitiendo identificar pacientes con alta probabilidad de metástasis incluso antes de manifestaciones clínicas evidentes. No obstante, persisten desafíos relacionados con la estandarización de métodos de cuantificación, la variabilidad entre plataformas analíticas y su aplicabilidad en diferentes contextos sanitarios. Los resultados revisados muestran que MACC1 representa un biomarcador prometedor para mejorar la precisión pronóstica en CCR, reforzando la necesidad de integrar su evaluación en futuras líneas diagnósticas y de investigación clínica para optimizar la identificación y manejo de pacientes con mayor riesgo metastásico.
Descargas
Citas
Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut [Internet]. 2023 Feb 1 [cited 2025 Oct 22];72(2):338–44. Available from: https://gut.bmj.com/content/72/2/338
Schöpe PC, Torke S, Kobelt D, Kortüm B, Treese C, Dumbani M, et al. MACC1 revisited – an in-depth review of a master of metastasis. Biomark Res [Internet]. 2024 Dec 1 [cited 2025 Oct 22];12(1):1–26. Available from: https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-024-00689-4
Vuaroqueaux V, Musch A, Kobelt D, Risch T, Herrmann P, Burock S, et al. Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival. Cancers (Basel) [Internet]. 2022 Apr 1 [cited 2025 Oct 22];14(7):1749. Available from: https://www.mdpi.com/2072-6694/14/7/1749
Erdem M, Lee KH, Hardt M, Regan JL, Kobelt D, Walther W, et al. MACC1 Regulates LGR5 to Promote Cancer Stem Cell Properties in Colorectal Cancer. Cancers 2024, Vol 16, Page 604 [Internet]. 2024 Jan 31 [cited 2025 Oct 25];16(3):604. Available from: https://www.mdpi.com/2072-6694/16/3/604
Hohmann T, Hohmann U, Dehghani F. MACC1-induced migration in tumors: Current state and perspective. Front Oncol [Internet]. 2023 Mar 27 [cited 2025 Oct 25];13:1165676. Available from: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1165676/full
Dahlmann M, Werner R, Kortüm B, Kobelt D, Walther W, Stein U. Restoring Treatment Response in Colorectal Cancer Cells by Targeting MACC1-Dependent ABCB1 Expression in Combination Therapy. Front Oncol [Internet]. 2020 Apr 23 [cited 2025 Oct 27];10:525805. Available from: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00599/full
Zhang Z, Jia H, Wang Y, Du B, Zhong J. Association of MACC1 expression with lymphatic metastasis in colorectal cancer: A nested case-control study. PLoS One [Internet]. 2021 Aug 1 [cited 2025 Oct 27];16(8):e0255489. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255489
Zhang M, Yang J, Jiang H, Jiang H, Wang Z. Correlation between glucose metabolism parameters derived from FDG and tumor TNM stages and metastasis-associated proteins in colorectal carcinoma patients. BMC Cancer [Internet]. 2021 Dec 1 [cited 2025 Nov 1];21(1):1–9. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07944-z
Zhou H, Liu Z, Wang Y, Wen X, Amador EH, Yuan L, et al. Colorectal liver metastasis: molecular mechanism and interventional therapy. Signal Transduct Target Ther [Internet]. 2022 Dec 1 [cited 2025 Nov 1];7(1):1–25. Available from: https://www.nature.com/articles/s41392-022-00922-2
Shao Z, Pan H, Tu S, Zhang J, Yan S, Shao A. HGF/c-Met Axis: The Advanced Development in Digestive System Cancer. Front Cell Dev Biol [Internet]. 2020 Oct 26 [cited 2025 Nov 1];8:520848. Available from: https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00801/full
Wen J, Xie Y, Zhang Y, Li J, Li J, Zhang Y, et al. MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability. Front Cell Dev Biol [Internet]. 2020 Dec 23 [cited 2025 Nov 1];8:513508. Available from: https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00825/full
Lv M, Jiao Y, Yang B, Ye M, Di W, Su W, et al. MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer. Biology 2023, Vol 12, Page 455 [Internet]. 2023 Mar 16 [cited 2025 Nov 5];12(3):455. Available from: https://www.mdpi.com/2079-7737/12/3/455
Li Q, Geng S, Luo H, Wang W, Mo YQ, Luo Q, et al. Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy. Signal Transduct Target Ther [Internet]. 2024 Dec 1 [cited 2025 Nov 5];9(1):1–48. Available from: https://www.nature.com/articles/s41392-024-01953-7
Kobelt D, Perez-Hernandez D, Fleuter C, Dahlmann M, Zincke F, Smith J, et al. The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis. Oncogene [Internet]. 2021 Aug 26 [cited 2025 Nov 10];40(34):5286–301. Available from: https://www.nature.com/articles/s41388-021-01917-z
Lisec J, Kobelt D, Walther W, Mokrizkij M, Grötzinger C, Jaeger C, et al. Systematic Identification of MACC1-Driven Metabolic Networks in Colorectal Cancer. Cancers 2021, Vol 13, Page 978 [Internet]. 2021 Feb 26 [cited 2025 Nov 10];13(5):978. Available from: https://www.mdpi.com/2072-6694/13/5/978
Li ZX, Xie Q, Wang BB, Yu DJ, Liu CF, Wang K, et al. A novel long noncoding RNA, AC005062.1, acts as an oncogene in colorectal cancer cell by regulating MACC1. SCIENCEASIA. 2023 Oct;49(4):595–602. DOI: doi.org/10.2306/scienceasia1513-1874.2023.058
Hu RH, Chuang CY, Lin CW, Su SC, Chang LC, Wu SW, et al. Effect of MACC1 Genetic Polymorphisms and Environmental Risk Factors in the Occurrence of Oral Squamous Cell Carcinoma. J Pers Med. 2021 Oct;11(6). DOI: doi.org/10.3390/jpm11060490
Hu Y, Wang ML, Wang KN, Gao JY, Tong JC, Zhao ZW, et al. A potential role for metastasis-associated in colon cancer 1 (MACC1) as a pan-cancer prognostic and immunological biomarker. MATHEMATICAL BIOSCIENCES AND ENGINEERING. 2021;18(6):8331–53. DOI: doi.org/10.3934/mbe.2021413
Mao X, Wang J, Luo F. Alpha-fetoprotein can promote gastric cancer progression via upregulation of metastasis-associated colon cancer 1. Oncol Lett. 2022 Oct;23(3). DOI: doi.org/10.3892/ol.2022.13204
Cheng H, Zhou LX, Long YL, Xiang JJ, Chen LH. MACC1 Is Associated With Epithelial-Mesenchymal Transition and Can Predict Poor Prognosis in Nasopharyngeal Carcinoma. Front Oncol. 2021 Oct;11. DOI: doi.org/10.3389/fonc.2021.644120
Xiong M, Wang MS, Yan YH, Chen XW, Guo WW, Xu M, et al. MACC1 Promotes the Progression and Is a Novel Biomarker for Predicting Immunotherapy Response in Colorectal Cancer. J Oncol. 2022 Oct;2022. DOI: doi.org/10.1155/2022/8326940
Hohmann T, Hohmann U, Kolbe MR, Dahlmann M, Kobelt D, Stein U, et al. MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma. CELL COMMUNICATION AND SIGNALING. 2020 Oct;18(1). DOI: doi.org/10.1186/s12964-020-00566-1
Liu BX, Yang J, Zeng CY, Chen YX. MACC1 Correlates with Tumor Progression and Immune Cell Infiltration of Colon Adenocarcinoma and is Regulated by the lncRNA ZFAS1/miR-642a-5p Axis. J Oncol. 2022 Oct;2022. DOI: doi.org/10.1155/2022/8179208
Mei J, Zhu CY, Pan LL, Li MA. MACC1 regulates the AKT/STAT3 signaling pathway to induce migration, invasion, cancer stemness, and suppress apoptosis in cervical cancer cells. Bioengineered. 2022 Oct;13(1):61–70. DOI: doi.org/10.1080/21655979.2021.2006567
Dillekås H, Rogers MS, Straume O. Are 90% of deaths from cancer caused by metastases? Cancer Med [Internet]. 2019 Sep 1 [cited 2025 Nov 18];8(12):5574–6. Available from: https://onlinelibrary.wiley.com/doi/10.1002/cam4.2474
Qian XT, Zhao YX, Zhang TY, Fan PS. Downregulation of MACC1 facilitates the reversal effect of verapamil on the chemoresistance to active metabolite of irinotecan in human colon cancer cells. Heliyon. 2022 Oct;8(11). DOI: doi.org/10.1016/j.heliyon.2022.e11294
Zheng G, You CJ, Qiu ZD, Zheng XN. Expression of MACC1 protein in gastric cancer and its effect on proliferation and invasion of gastric cancer cells. Cell Mol Biol. 2020;66(2):111–7. DOI: doi.org/10.14715/cmb/2020.66.2.18
Wang LJ, Fan LY, Xu HY, Jiang HY. Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer A protocol for systematic review and meta-analysis. Medicine. 2021 Oct;100(8). DOI: doi.org/10.1097/MD.0000000000024255
Lv MM, Jiao YJ, Yang BW, Ye MC, Di WY, Su W, et al. MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer. BIOLOGY-BASEL. 2023 Oct;12(3). DOI: doi.org/10.3390/BIOLOGY12030455
Vuaroqueaux V, Musch A, Kobelt D, Risch T, Herrmann P, Burock S, et al. Elevated MACC1 Expression in Colorectal Cancer Is Driven by Chromosomal Instability and Is Associated with Molecular Subtype and Worse Patient Survival. Cancers (Basel). 2022 Oct;14(7). DOI: doi.org/10.3390/cancers14071749
Schmid F, Dahlmann M, Rhrich H, Kobelt D, Hoffmann J, Burock S, et al. Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker. Br J Cancer. 2022 Oct;127(4):675–85. DOI: doi.org/10.1038/s41416-022-01833-3
Juneja M, Kobelt D, Walther W, Voss C, Smith J, Specker E, et al. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol [Internet]. 2017 Jun 1 [cited 2025 Dec 7];15(6):e2000784. Available from: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2000784
Pan CQ, Wu JH, Zheng ST, Sun HY, Fang YS, Huang ZH, et al. Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β2-AR/MACC1 axis. Cancer Commun. 2021 Oct;41(10):1049–70.
Kobelt D, Perez-Hernandez D, Fleuter C, Dahlmann M, Zincke F, Smith J, et al. The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis. Oncogene. 2021 Oct;40(34):5286–301. DOI: doi.org/10.1038/s41388-021-01917-z
Ahmed M, Aslam M. Serum MACC-1: a new biomarker for breast cancer. Oncotarget [Internet]. 2020;11(48):4521–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721609
Ali DA, El-Guindy DM, Elrashidy MA, Sabry NM, Kabel AM, Gaber RA, et al. The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival. MEDICINA-LITHUANIA. 2021 Oct;57(9). DOI: doi.org/10.3390/medicina57090934
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2026 Revista Científica de Salud BIOSANA

Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.




