Evaluation of Epigenetic Markers in the Diagnosis and Prognosis of Colorectal Cancer

Authors

DOI:

https://doi.org/10.56294/saludcyt20251139

Keywords:

Colorectal Neoplasms, Colorectal Cancer, Epigenesis, Genetics

Abstract

Introduction: colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Epigenetic factors play a significant role in its development and are increasingly used as tools for early diagnosis and prognosis of this disease.

Method: a literature review was conducted on studies published in the last 10 years, available in databases such as PubMed, Cochrane, and SciELO. The selected studies analyze the effectiveness of epigenetic markers, such as DNA methylation and microRNAs, in CRC detection and prognosis.

Results: out of 112 articles reviewed, 45 studies met the inclusion criteria, excluding duplicates and those that did not align with the objectives of this review. The analyzed studies highlight that epigenetic marker, particularly the methylation of genes such as SEPT9, NDRG4, and BMP3, are effective in detecting colorectal cancer (CRC) in its early stages, thus enhancing early intervention opportunities. Key microRNAs, such as miR-21, miR-92a, and miR-29a, were also identified, with their alteration associated with CRC progression and aggression prediction.

Conclusions: epigenetic markers provide valuable insights into tumor behavior, metastatic potential, and response to various treatment modalities. Some of the most recent studies suggest that the combined use of epigenetic biomarkers and traditional screening methods, such as colonoscopy, may optimize diagnostic accuracy.

References

Lao VV, Grady WM. Epigenetics and colorectal cancer. Nature Reviews Gastroenterology & Hepatology. 2011;8(12):686-700. https://doi.org/10.1038/nrgastro.2011.173

Viñes J, Ardanaz E, Arrazola A, Gaminde I, José Javier Viñes Rueda C. Epidemiología poblacional de cáncer colorrectal: revisión de la causalidad. An Sist Sanit Navar. 2003;26(1):79-97. https://doi.org/10.4321/s1137-66272003000100007

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-91. https://doi.org/10.1136/gutjnl-2015-310912

Jung G, Hernández-Illán E, Moreira L, Balaguer F, Goel A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nature Reviews Gastroenterology & Hepatology. 2020;17(2):111-30. https://doi.org/10.1038/s41575-019-0243-4

Okugawa Y, Grady WM, Goel A. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. Gastroenterology. 2015;149(5):1204-1225.e12. https://doi.org/10.1053/j.gastro.2015.07.011

Puccini A, Berger MD, Naseem M, Tokunaga R, Battaglin F, Cao S, et al. Colorectal cancer: epigenetic alterations and their clinical implications. Biochim Biophys Acta Rev Cancer. 2017;1868(2):439-48. https://doi.org/10.1016/j.bbcan.2017.07.003

Hong SN. Genetic and epigenetic alterations of colorectal cancer. Intest Res. 2018;16(3):327-37. https://doi.org/10.5217/ir.2018.16.3.327

Coppedè F, Lopomo A, Spisni R, Migliore L. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol. 2014;20(4):943-56. https://doi.org/10.3748/wjg.v20.i4.943

Afanador CH, Palacio KA, Isaza LF, Ahumada E, Ocampo CM, Muñetón CM, et al. Caracterización molecular de pacientes con cáncer colorrectal. Biomédica. 2022;42:154-71. https://doi.org/10.7705/biomedica.5798

Skopelitou D, Miao B, Srivastava A, Kumar A, Kuswick M, Dymerska D, et al. Whole Exome Sequencing Identifies APCDD1 and HDAC5 Genes as Potentially Cancer Predisposing in Familial Colorectal Cancer. Int J Mol Sci. 2021;22(4):1-23. https://doi.org/10.3390/ijms22041762

Barnell EK, Wurtzler EM, La Rocca J, Fitzgerald T, Petrone J, Hao Y, et al. Multitarget Stool RNA Test for Colorectal Cancer Screening. JAMA. 2023;330(18):1760-8. https://doi.org/10.1001/jama.2023.17654

Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97(3):683-701. https://doi.org/10.1016/j.suc.2017.01.009

Luo M, Yang X, Chen HN, Nice EC, Huang C. Drug resistance in colorectal cancer: An epigenetic overview. Biochim Biophys Acta Rev Cancer. 2021;1876(2):188623. https://doi.org/10.1016/j.bbcan.2021.188623

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372. https://doi.org/10.1136/bmj.n71

Schreuders EH, Grobbee E, Roon AR, van Dam L, Zauber A, Lansdorp-Vogelaar I, et al. Meta-analysis on guaiac-based fecal occult blood tests versus fecal immunochemical tests for colorectal cancer screening. Gastroenterology.2016;150(4). https://doi.org/10.1016/s0016-5085(16)32233-8

Kupper BC, Junior SA, Nakagawa WT, Takahashi R, Batista RSS, Bezerra T, et al. Comparison between an immunochemical fecal occult blood test and a guaiac based fecal occult blood test in detection of adenomas and colorectal cancer. Appl Cancer Res. 2018;38:56. https://doi.org/10.1186/s41241-018-0056-x

Nieuwenburg S, Mommersteeg M, Wolters L, van Vuuren AV, Erler N, Peppelenbosch M, et al. Accuracy of H. pylori fecal antigen test using fecal immunochemical test (FIT). Gastric Cancer. 2021;24(6):1047-1054. https://doi.org/10.1007/s10120-021-01264-8

Kapidzic A, Grobbee E, Hol L, van Roon AR, van Vuuren AV, Spijker W, et al. Attendance and yield over three rounds of population-based fecal immunochemical test screening. Am J Gastroenterol. 2014;109(8):1257-64. https://doi.org/10.1038/ajg.2014.168

Naganuma M, Kanai T. Reply: Fecal immunochemical test, in addition to the fecal calprotectin test, is useful for assessing the disease severity. Clin Gastroenterol Hepatol. 2019;17(11):2289-90. https://doi.org/10.1016/j.cgh.2019.09.015

Yamaji Y, Watanabe Y, Wada R. False-positive fecal immunochemical tests in users of new anticoagulants. Gastroenterology. 2019;157(3):746-7. https://doi.org/10.1053/j.gastro.2019.06.042

Sanders D, Bakos B, Lovedeep G, Gentile L, Telford J. Physician factors associated with inappropriate fecal immunochemical testing. JCAG. 2018;1(Suppl_2):373. https://doi.org/10.1093/JCAG/GWY009.259

Hanna M, Dey N, Grady W. Emerging tests for noninvasive colorectal cancer screening. Clin Gastroenterol Hepatol. 2022;21(1):60-71. https://doi.org/10.1016/j.cgh.2022.12.008

Dickerson L, Varcak SC. Colorectal cancer screening: the role of the noninvasive options. JAAPA. 2016;29(9):1-5. https://doi.org/10.1097/01.JAA.0000490946.35987.58

Bailey JR, Aggarwal A, Imperiale T. Colorectal cancer screening: stool DNA and other noninvasive modalities. Gut Liver. 2016;10(2):204-9. https://doi.org/10.5009/gnl15420

Lin K. mSEPT9 (Epi proColon) blood test for colorectal cancer screening. PubMed. 2019;31259500. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31259500

Vereshchak V, Iurichev IN, Rasulov AO, Madyarov J. Noninvasive colorectal cancer screening techniques: literature review. MD Onco. 2023;3(3):57-63. https://doi.org/10.17650/2782-3202-2023-3-3-57-63

Lye KL, Tan LT, Yap H. Insight of microRNA role in colorectal cancer. Proc Microb Mol Biol. 2020;1:286-92. https://doi.org/10.36877/pmmb.a0000083

Falzone L, Scola L, Zanghì A, Biondi A, Di Cataldo A, Libra M, et al. Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development. Aging (Albany NY). 2018;10(5):1000-14. https://doi.org/10.18632/aging.101444

Gmerek L, Martyniak K, Horbacka K, Krokowicz P, Ścierski W, Golusiński P, et al. MicroRNA regulation in colorectal cancer tissue and serum. PLoS One. 2019;14(8). https://doi.org/10.1371/journal.pone.0222013

Chu D, Zheng J, Li J, Li YM, Zhang J, Zhao Q, et al. MicroRNA-630 is a prognostic marker for patients with colorectal cancer. Tumor Biol. 2014;35(7):6633-7. https://doi.org/10.1007/s13277-014-2223-3

Yamada A, Yu P, Lin W, Okugawa Y, Boland C, Goel A. A RNA-Sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer. Sci Rep. 2018;8(1):5657. https://doi.org/10.1038/s41598-017-18407-6

Jing F, Jin H, Mao Y, Li Y, Ding Y, Fan C, et al. Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer. Tumor Biol. 2017;39(4):1010428317703650. https://doi.org/10.1177/1010428317703650

Weng M, Wu D, Yang C, Peng H, Wang G, Wang T, et al. Noncoding RNAs in the development, diagnosis, and prognosis of colorectal cancer. Transl Res. 2017;190:62-74. https://doi.org/10.1016/j.trsl.2016.10.001

Ruiz-Bañobre J, Rodríguez-Casanova A, Costa-Fraga N, Bao-Caamano A, Álvarez-Castro A, Carreras-Presas M, et al. Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA. Clin Epigenetics. 2022;14(1):101. https://doi.org/10.1186/s13148-022-01302-x

Bjerrum A, Andersen O, Fischer A, et al. Biomarkers for Colorectal Cancer Detection. BMJ Open Gastroenterol. 2016;3(1). https://doi.org/10.1136/bmjgast-2015-000079

Ebell MH. FIT More Acceptable with Better Detection Rate Than gFOBT for Colorectal Cancer Screening. Am Fam Physician. 2018;97(12):818-20.

Almansoori A, Alzaabi M, Alketbi L. Colorectal Cancer Screening in Ambulatory Healthcare Service Clinics in Abu Dhabi, United Arab Emirates in 2015-2016. BMC Cancer. 2021;21(1):897. https://doi.org/10.1186/s12885-021-08623-9

Bevan R, Rutter MD. Colorectal Cancer Screening-Who, How, and When? Clin Endosc. 2018;51(1):37-49. https://doi.org/10.5946/ce.2017.141

Tinmouth J, Vella ET, Baxter NN, Dubé C, Gould M, Hey A, et al. Colorectal Cancer Screening in Average Risk Populations: Evidence Summary. Can J Gastroenterol Hepatol. 2016;2016:2878149. https://doi.org/10.1155/2016/2878149

Tepus M, Yau TO. Non-Invasive Colorectal Cancer Screening: An Overview. Gastrointest Tumors. 2020;7(3):62-73. https://doi.org/10.1159/000507701

Cleback KT, Nickolich S, Mendez-Miller M. Multitarget Stool DNA Testing (Cologuard) for Colorectal Cancer Screening. Am Fam Physician. 2022;105(2):198-200.

Chablani SV, Cohen N, White D, Itzkowitz SH, DuHamel K, Jandorf L. Colorectal Cancer Screening Preferences among Black and Latino Primary Care Patients. J Immigr Minor Health. 2017;19(5):1100-1108. https://doi.org/10.1007/s10903-016-0453-8

Arredondo-Valdez AR, Wence-Chavez L, Rosales-Reynoso MA. Utilidad de los microARN en el diagnóstico y pronóstico del cáncer colorrectal. Gac Med Mex. 2016;152(3):386-9.

Müller D, Győrffy B. DNA methylation-based diagnostic, prognostic, and predictive biomarkers in colorectal cancer. Biochim Biophys Acta Rev Cancer. 2022;1877(3):188722. https://doi.org/10.1016/j.bbcan.2022.188722

Wang Y, Zhang Y, Wang F, Li T, Song X, Shi H, et al. Bioinformatics analysis of prognostic value and immunological role of MeCP2 in pan-cancer. Sci Rep. 2022;12(1):18518. https://doi.org/10.1038/s41598-022-21328-8

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Published

2025-01-01

How to Cite

1.
Ruiz-Quinga AA, Noriega-Puga VR. Evaluation of Epigenetic Markers in the Diagnosis and Prognosis of Colorectal Cancer. Salud, Ciencia y Tecnología [Internet]. 2025 Jan. 1 [cited 2024 Dec. 10];5:1139. Available from: https://sct.ageditor.ar/index.php/sct/article/view/1139