Evidence map›Paper›PMID 40334314›Full record

ArticleESMO open2025

Genome-wide DNA methylation status as a biomarker for clinical outcomes of first-line treatment in patients with RAS wild-type metastatic colorectal cancer: JACCRO CC-13AR.

K Ouchi, Y Sunakawa, A Tsuji, M Shiozawa, T Kawai, H Yasui, H Ota, M Kochi, D Manaka, H Ohori and 9 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. 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

19 authors.

K OuchiDepartment of Medical Oncology, Tohoku University Hospital, Sendai, Japan.
Y SunakawaDepartment of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. Electronic address: y.suna0825@gmail.com.
A TsujiDepartment of Clinical Oncology, Faculty of Medicine, Kagawa University, Miki-Gun, Japan.
M ShiozawaDepartment of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
T KawaiDepartment of Surgery, Japanese Red Cross Society Himeji Hospital, Himeji, Japan.
H YasuiDepartment of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
H OtaDepartment of Gastroenterological Surgery, Ikeda City Hospital, Ikeda, Japan.
M KochiDepartment of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
D ManakaDepartment of Surgery, Gastro-Intestinal Center, Kyoto Katsura Hospital, Kyoto, Japan.
H OhoriDepartment of Medical Oncology, Ishinomaki Red Cross Hospital, Ishinomaki, Japan.
T MiyakeDepartment of Surgery, Shiga University of Medical Science Hospital, Otsu, Japan.
T YamaguchiDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
M MatsuuraDepartment of Surgery, Nishikobe Medical Center, Kobe, Japan.
T SagawaDivision of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
A MakiyamaCancer Center, Gifu University Hospital, Gifu, Japan.
M TakeuchiGraduate School of Mathematical Sciences, The University of Tokyo, Tokyo, Japan.
W IchikawaDivision of Medical Oncology, Showa University Fujigaoka Hospital, Kanagawa, Japan.
M FujiiJapan Clinical Cancer Research Organization, Tokyo, Japan.
C IshiokaDepartment of Medical Oncology, Tohoku University Hospital, Sendai, Japan; JR Sendai Hospital, Sendai, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSeveral retrospective studies have demonstrated an association between genome-wide DNA methylation status (GWMS) and clinical outcomes after treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (mCRC). This biomarker study evaluated the association of GWMS with clinical outcomes in mCRC patients who were enrolled in a randomized phase II DEEPER trial of comparing modified (m)-FOLFOXIRI plus bevacizumab (Bev) and m-FOLFOXIRI plus cetuximab (Cet) as first-line treatment. PATIENTS AND

methodsGWMS was measured using tumor tissues which were collected from patients with tissue samples available in the DEEPER trial. In addition, tumor tissues were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC) groups. The correlation between GWMS and survival was analyzed by comparing progression-free survival (PFS) and overall survival (OS) between the two different groups of GWMS.

resultsOf the 137 patients, 15 were classified into the HMCC group, and 122 were classified into the LMCC group; 71 patients were treated with Bev, and 66 were treated with Cet. In the Bev arm, OS was significantly shorter in the HMCC group than in the LMCC group (median 24.2 versus 48.9 months, P = 0.03). In the Cet arm, both PFS and OS were significantly shorter in the HMCC group than in the LMCC group (median 4.0 versus 14.3 months, P < 0.01 and median 13.6 versus 42.7 months, P < 0.01). The interaction tests revealed that GWMS was a significant predictor of PFS and OS in the Cet arm.

conclusionsGWMS was associated with survival in RAS wild-type mCRC patients treated with initial chemotherapy. Also, it may serve as a predictor for selection of molecular-targeted antibodies in first-line treatment.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorColorectal NeoplasmsDNA MethylationAgedBevacizumabCetuximabClinical Trials, Phase III as TopicFemaleFluorouracilHumansLeucovorinMaleMiddle AgedNeoplasm MetastasisRandomized Controlled Trials as TopicBevacizumabBiomarkers, TumorCetuximabFluorouracilLeucovorinanti-EGFR treatmentbiomarkercolorectal cancergenome-wide DNA methylation statuspredictive factor

Identifiers

PMID40334314
PMCPMC12167864

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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.