Evidence map›Paper›PMID 35810318›Full record

ArticleClinical epigenetics2022

Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA.

Juan Ruiz-Bañobre, Aitor Rodriguez-Casanova, Nicolas Costa-Fraga, Aida Bao-Caamano, Ana Alvarez-Castro, Martín Carreras-Presas, Elena Brozos-Vazquez, Yolanda Vidal-Insua, Francisca Vazquez-Rivera, Sonia Candamio-Folgar and 14 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review: Detection of Cancer Biomarkers from a Clinical Perspective.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Article
  7. Advances in laboratory medicine · 2025
    Article
  8. Review
  9. UnravelingInternational journal of molecular sciences · 2025
    Article
  10. Methylation ofAdvanced biomedical research · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 8 institutions in 2 countries.

Juan Ruiz-Bañobre *Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Aitor Rodriguez-Casanova *Cancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Nicolas Costa-FragaCancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Aida Bao-CaamanoCancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Ana Alvarez-CastroDepartment of Gastroenterology and Hepatology, University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Martín Carreras-PresasDepartment of Gastroenterology and Hepatology, University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Elena Brozos-VazquezTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Yolanda Vidal-InsuaTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Francisca Vazquez-RiveraTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Sonia Candamio-FolgarTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Manuel Mosquera-PresedoCancer Epigenomics Laboratory, Epigenomics Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Ramón M Lago-LestónLiquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain.
Laura Muinelo-RomayCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain.
José Ángel Vázquez-BuenoDepartment of Pathology, Complejo Hospitalario Universitario de Ferrol (SERGAS), 15405, Ferrol, Spain.
Rebeca Sanz-PamplonaUnit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08907, Barcelona, Spain.
Víctor MorenoUnit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), 08907, Barcelona, Spain.
Ajay GoelCenter for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott and White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Lourdes CastilloAdvanced Marker Discovery (AMADIX), 47004, Valladolid, Spain.
Ana C MartinAdvanced Marker Discovery (AMADIX), 47004, Valladolid, Spain.
Rocio ArroyoAdvanced Marker Discovery (AMADIX), 47004, Valladolid, Spain.
Manel EstellerCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain.
Ana B CrujeirasEpigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain.
Rafael López-LópezTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706, Santiago de Compostela, Spain. rafael.lopez.lopez@sergas.es.
Angel Díaz-LagaresCentro de Investigación Biomédica en Red Cáncer (CIBERONC), ISCIII, 28029, Madrid, Spain. angel.diaz.lagares@sergas.es.
Servicio Gallego de Salud · ESInstituto de Investigación Sanitaria de Santiago · ESInstituto de Salud Carlos III · ESBeckman Research InstituteCentre for Biomedical Network Research on Rare Diseases · ESInstitut Català d'Oncologia · ESRoche (Spain) · ESUniversidade de Santiago de Compostela · ES

Funding

Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic CancerU01CA214254 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Ajay Goel, DANIEL D VON HOFF · 2017 to 2026
$8.9M
MicroRNA Biomarkers for Determining Treatment Response in Colorectal CancerR01CA202797 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2016 to 2020
$1.9M
Development of microRNA Biomarkers For Noninvasive Detection of Colorectal CancerR01CA184792 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2015 to 2019
$1.8M
METHYLATION BIOMARKER DEVELOPMENT FOR NONINVASIVE DETECTION OF COLORECTAL CANCERR01CA181572 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI GOEL, AJAY · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA181572NCI NIH HHS R01 CA184792NCI NIH HHS R01 CA202797NCI NIH HHS U01 CA214254
6 · The paper itself

Abstract

backgroundCurrent noninvasive assays have limitations in the early detection of colorectal cancer. We evaluated the clinical utility of promoter methylation of the long noncoding RNA LINC00473 as a noninvasive biomarker to detect colorectal cancer and associated precancerous lesions.

methodsWe evaluated the epigenetic regulation of LINC00473 through promoter hypermethylation in colorectal cancer cell lines using bisulfite genomic sequencing and expression analyses. DNA methylation of LINC00473 was analyzed in primary colorectal tumors using 450K arrays and RNA-seq from The Cancer Genome Atlas (TCGA). Tissue-based findings were validated in several independent cohorts of colorectal cancer and advanced colorectal polyp patients by pyrosequencing. We explored the clinical utility of LINC00473 methylation for the early detection of colorectal cancer in plasma cell-free DNA by quantitative methylation-specific PCR and droplet digital PCR.

resultsLINC00473 showed transcriptionally silencing due to promoter hypermethylation in colorectal cancer cell lines and primary tumors. Methylation of the LINC00473 promoter accurately detected primary colorectal tumors in two independent clinical cohorts, with areas under the receiver operating characteristic curves (AUCs) of 0.94 and 0.89. This biomarker also identified advanced colorectal polyps from two other tissue-based clinical cohorts with high diagnostic accuracy (AUCs of 0.99 and 0.78). Finally, methylation analysis of the LINC00473 promoter in plasma cell-free DNA accurately identified patients with colorectal cancer and advanced colorectal polyps (AUCs of 0.88 and 0.84, respectively), which was confirmed in an independent cohort of patients.

conclusionsHypermethylation of the LINC00473 promoter is a new promising biomarker for noninvasive early detection of colorectal cancer and related precancerous lesions.

Indexed as

Cell-Free Nucleic AcidsColonic PolypsColorectal NeoplasmsPrecancerous ConditionsBiomarkers, TumorDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansBiomarkers, TumorCell-Free Nucleic AcidsCell-free DNAColorectal cancerDNA methylationEarly detectionLINC00473

Identifiers

PMID35810318
PMCPMC9271259
OpenAlexW4284966854

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