# DNA Methylation in Urine and Feces Indicative of Eight Major Human Cancer Types Globally

**Authors:** Melanie Engstrom Newell, Ayesha Babbrah, Anumitha Aravindan, Raj Rathnam, Rolf U. Halden

PMC · DOI: 10.3390/life15030482 · Life · 2025-03-17

## TL;DR

This paper shows that DNA methylation in urine and feces can detect eight major cancers globally, with potential for large-scale monitoring.

## Contribution

The study compiles and evaluates epigenetic biomarkers in urine and feces for cancer detection across global regions.

## Key findings

- Epigenetic biomarkers in urine and feces show high sensitivity and specificity for detecting gastric and urinary cancers.
- Biomarker panels like SEPT9 and combinations of GDF15, TMEFF2, and VIM demonstrate strong diagnostic potential.
- Data on epigenetic biomarkers are limited in regions with high cancer incidence, such as New Zealand and Japan.

## Abstract

Toxic chemicals and epigenetic biomarkers associated with cancer have been used successfully in clinical diagnostic screening of feces and urine from individuals, but they have been underutilized in a global setting. We analyzed peer-reviewed literature to achieve the following: (i) compile epigenetic biomarkers of disease, (ii) explore whether research locations are geographically aligned with disease hotspots, and (iii) determine the potential for tracking disease-associated epigenetic biomarkers. Studies (n = 1145) of epigenetic biomarkers (n = 146) in urine and feces from individuals have established notable diagnostic potential for detecting and tracking primarily gastric and urinary cancers. Panels with the highest sensitivity and specificity reported more than once were SEPT9 (78% and 93%, respectively) and the binary biomarker combinations GDF15, TMEFF2, and VIM (93% and 95%), NDRG4 and BMP3 (98% and 90%), and TWIST1 and NID2 (76% and 79%). Screening for epigenetic biomarkers has focused on biospecimens from the U.S., Europe, and East Asia, whereas data are limited in regions with similar/higher disease incidence rates (i.e., data for New Zealand, Japan, and Australia for colorectal cancer). The epigenetic markers discussed here may aid in the future monitoring of multiple cancers from individual- to population-level scales by leveraging the emerging science of wastewater-based epidemiology (WBE).

## Linked entities

- **Genes:** SEPTIN9 (septin 9) [NCBI Gene 10801], GDF15 (growth differentiation factor 15) [NCBI Gene 9518], TMEFF2 (transmembrane protein with EGF like and two follistatin like domains 2) [NCBI Gene 23671], VIM (vimentin) [NCBI Gene 7431], NDRG4 (NDRG family member 4) [NCBI Gene 65009], BMP3 (bone morphogenetic protein 3) [NCBI Gene 651], TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291], NID2 (nidogen 2) [NCBI Gene 22795]
- **Diseases:** gastric cancer (MONDO:0001056), colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** TMEFF2 (transmembrane protein with EGF like and two follistatin like domains 2) [NCBI Gene 23671] {aka CT120.2, HPP1, TENB2, TPEF, TR, TR-2}, BMP3 (bone morphogenetic protein 3) [NCBI Gene 651] {aka BMP-3A}, VIM (vimentin) [NCBI Gene 7431], GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, NID2 (nidogen 2) [NCBI Gene 22795] {aka NID-2}, NDRG4 (NDRG family member 4) [NCBI Gene 65009] {aka BDM1, SMAP-8, SMAP8}, SEPTIN9 (septin 9) [NCBI Gene 10801] {aka AF17q25, MSF, MSF1, PNUTL4, SEPT9, SINT1}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}
- **Diseases:** gastric and urinary cancers (MESH:D013274), Cancer (MESH:D009369), colorectal cancer (MESH:D015179), Toxic (MESH:D064420)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11943902/full.md

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11943902/full.md

## References

119 references — full list in the complete paper: https://tomesphere.com/paper/PMC11943902/full.md

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Source: https://tomesphere.com/paper/PMC11943902