Evidence map›Paper›PMID 36171645›Full record

ArticleJournal of the National Cancer Institute2023

DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer.

Huichuan Yu, Xiaolin Wang, Liangliang Bai, Guannan Tang, Kelly T Carter, Ji Cui, Pinzhu Huang, Li Liang, Yanqing Ding, Muyan Cai and 11 more

Abstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
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

21 authors.

Huichuan YuDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Xiaolin WangGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Liangliang BaiGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Guannan TangGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Kelly T CarterClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Ji CuiDepartments of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Pinzhu HuangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Li LiangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yanqing DingDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Muyan CaiState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Meijin HuangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Huanliang LiuGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Guangwen CaoDepartment of Epidemiology, Second Military Medical University, Shanghai, China.ORCID 0000-0002-8094-1278
Steven GallingerWallace McCain Centre for Pancreatic Cancer, Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Rish K PaiDepartment of laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.ORCID 0000-0002-2692-221X
Daniel D BuchananColorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
Aung Ko WinCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
Polly A NewcombDepartment of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
Jianping WangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
William M GradyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Yanxin LuoDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.ORCID 0000-0002-5200-3997

Funding

Transdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare StudyU01CA206110 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jane C. Figueiredo, Christopher I Li · 2016 to 2026
$18.6M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
Biomarkers for optimizing risk prediction and early detection of cancers of the colon and esophagusU2CCA271902 · NCI · FRED HUTCHINSON CANCER CENTER · PI William Mallory Grady · 2022 to 2026
$5.3M
(PQ6) Radiogenomics of colorectal polyps to assess benign proliferative vs. premalignant states.R01CA220004 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRADY, WILLIAM MALLORY, HALBERG, RICHARD BROTT · 2017 to 2021
$3.2M
(PQC1) Accelerated biological aging and colon polyp to cancer progressionR01CA194663 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRADY, WILLIAM MALLORY · 2015 to 2018
$1.6M
NCI NIH HHS R01 CA194663NCI NIH HHS R01 CA220004NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA206110NCI NIH HHS U2C CA271902NIH HHS RO1CA194663NIH HHS U01 CA167551
6 · The paper itself

Abstract

backgroundThe current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients.

methodsWe analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis. The machine-learning approach was applied to construct a DNA methylation-based prognostic classifier for early-stage CRC (MePEC) using the 4 gene methylation markers FAT3, KAZN, TLE4, and DUSP3. The prognostic value of the classifier was evaluated in 2 independent cohorts (n = 438 and 359, respectively).

resultsThe comprehensive analysis identified an epigenetic subtype with high risk of recurrence based on a group of CpG loci in the CpG-depleted region. In multivariable analysis, the MePEC classifier was independently and statistically significantly associated with time to recurrence in validation cohort 1 (hazard ratio = 2.35, 95% confidence interval = 1.47 to 3.76, P < .001) and cohort 2 (hazard ratio = 3.20, 95% confidence interval = 1.92 to 5.33, P < .001). All results were further confirmed after each cohort was stratified by clinicopathological variables and molecular subtypes.

conclusionsWe demonstrated the prognostic statistical significance of a DNA methylation profile in the CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC.

Indexed as

Colorectal NeoplasmsBiomarkers, TumorCinnamatesCpG IslandsDNA MethylationHumansPrognosisProportional Hazards Models2-methylphenyl 4-ethoxycinnamateBiomarkers, TumorCinnamates

Identifiers

PMID36171645
PMCPMC10089593

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.