Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 22;40(1):125.
doi: 10.1007/s00384-025-04904-y.

Diagnostic value of genetic and epigenetic biomarker panels for colorectal cancer detection: a systematic review

Georgios Alampritis #  1   2 , Sarah Nohelia Thoukididou #  1   2 , Maria Ramos  3 , Pantelis Georgiou  3 , Melpomeni Kalofonou  3 , Constantinos Simillis  4   5
Affiliations

Diagnostic value of genetic and epigenetic biomarker panels for colorectal cancer detection: a systematic review

Georgios Alampritis et al. Int J Colorectal Dis. .

Abstract

Purpose: Exploration of effective screening methods is imperative to improve current screening for colorectal cancer (CRC). Our aim was to systematically search the literature to identify and assess the diagnostic accuracy of both genetic and epigenetic biomarker panels for CRC detection using liquid biopsies for circulating tumour DNA (ctDNA) from stool, blood, or urine.

Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) with searches in Medline, Embase, CENTRAL, and Web Of Science from inception up to March 20, 2025, using pre-defined keywords. Study quality assessment was performed using QUADAS-2 tool (Quality Assessment for Diagnostic Accuracy Studies 2). Primary and secondary outcomes were panel performance (sensitivity and specificity) for CRC, advanced precancerous lesions (APL), and staging of disease.

Results: Forty-four studies were included. Exceptional performance for both CRC (sensitivity and specificity) and APL (sensitivity) was displayed by biomarker panels including methylated SDC2 with methylated SFRP1/2 (CRC: 91.5%/97.3%, APL: 89.2%) or methylated TFPI2 (CRC: 94.9%/98.1%, APL: 100%), and a 5-biomarker panel of mutational targets APC, Bat-26, KRAS, L-DNA, and p53 (CRC: 91.0%/93.0%, APL: 82.0%). Suboptimal APL sensitivities up to 57.0% were exhibited by Cologuard and variant panels (including KRAS, methylated BMP3, methylated NDRG4, FIT), and 47.8% for combinations including methylated SEPT9.

Conclusions: High-performance, candidate ctDNA biomarker panels with exceptional diagnostic accuracy for both CRC and APL have been identified. Further work should focus on the development of large-scale studies to justify their clinical implementation.

Keywords: Biomarker panels; Colorectal cancer; CtDNA; Detection; Epigenetic; Genetic.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the inclusion of the studies
Fig. 2
Fig. 2
Risk of bias and applicability concerns summary: review authors’ judgements about each domain for each included study
Fig. 3
Fig. 3
Risk of bias and applicability concerns graph: review authors’ judgements about each domain presented as percentages and counts across included studies
Fig. 4
Fig. 4
Count and percentage of different ctDNA analysis methods amongst studies. ctDNA = circulating tumour DNA, PCR = polymerase chain reaction, qPCR = quantitative PCR, MSP = methylation specific PCR, qMSP = quantitative methylation specific PCR, ddMethyLight PCR = droplet digital MethyLight PCR, MCTA-Seq = methylated CpG tandem amplification and sequencing, AS-qPCR = allele specific-quantitative PCR, NGS = next-generation sequencing, QuARTS = quantitative allele-specific real-time target and signal amplification, RT-qPCR = reverse transcription-quantitative PCR
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. 10.3322/CAAC.21660 - PubMed
    1. Bray F, Soerjomataram I (2015) The changing global burden of cancer: transitions in human development and implications for cancer prevention and control. Disease Control Priorities, 3rd Edition vol 3, Cancer, pp 23–44. 10.1596/978-1-4648-0349-9_CH2 - PubMed
    1. Fidler MM, Soerjomataram I, Bray F (2016) A global view on cancer incidence and national levels of the human development index. Int J Cancer 139:2436–2446. 10.1002/IJC.30382 - PubMed
    1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC et al (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70:145–164. 10.3322/CAAC.21601 - PubMed
    1. Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN et al (2010) Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 116:544–573. 10.1002/CNCR.24760 - PMC - PubMed

Publication types

Substances