Evidence map›Paper›PMID 33386473›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021

Alteration in stemness causes exclusivity between Epstein-Barr virus-positivity and microsatellite instability status in gastric cancer.

Younghoon Kim, Yun-Joo Shin, Xianyu Wen, Nam-Yun Cho, Meihui Li, Yun-Jee Kim, Sang Hyun Song, Gyeong Hoon Kang

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 44% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. The oncogenic role of hypomethylated ZNF793 in gastric carcinoma: a focus on cell survival and stemness.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Article
  2. Therapeutic opportunities in EBV-positive gastric cancer subtypes.Therapeutic advances in medical oncology · 2025
    Review
  3. Article
  4. 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

8 authors at 3 institutions in 5 countries.

Younghoon KimLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Yun-Joo ShinLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Xianyu WenGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Nam-Yun ChoLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Meihui LiLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Yun-Jee KimDepartment of Molecular Medicine and Biopharmaceutical Sciences, Cancer Research Center, Seoul National University College of Medicine, Seoul, South Korea.
Sang Hyun SongDepartment of Molecular Medicine and Biopharmaceutical Sciences, Cancer Research Center, Seoul National University College of Medicine, Seoul, South Korea.
Gyeong Hoon KangLaboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. ghkang@snu.ac.kr.ORCID http://orcid.org/0000-0003-2380-6675
Seoul National University · KRCancer Research Institute · USSun Yat-sen University · CN

Funding

Ministry of Education, Science and Technology 2016M3A9B6026921Ministry of Education, Science and Technology (KR) 2019R1F1A1061227Seoul National University Hospital (KR) 0320190010
6 · The paper itself

Abstract

backgroundGastric cancer (GC) is a leading cause of cancer morbidity and mortality worldwide. This is due to the heterogeneous features of GC, which consist of a diverse molecular phenotype. Epstein-Barr virus (EBV)-positive GC and microsatellite instability (MSI)-high GC encompass similar epigenetic traits, including high levels of DNA methylation in CpG islands; however, EBV-positive and MSI-high GCs are mutually exclusive. We aimed to elucidate the underlying mechanism of this exclusivity.

methodsWe knocked out MLH1 in EBV-positive GC cell lines SNU-719 and NCC24 via CRISPR-Cas9, and evaluated the modified cellular properties in vitro and in vivo. The MSI status of each cell line was screened with two marker capillary electrophoresis, and further diagnosed with five marker capillary electrophoresis and parallel sequencing using 21 markers.

resultsInitial evaluation showed that cell growth, migration, invasion, and MSI status were not affected by MLH1 silencing. However, with prolonged passage, GC cell lines gradually gained MSI and NCC24 cells were transformed to EBV-positive/MSI-high GC cells after 12 months. Furthermore, MLH1 silencing reduced tumor stemness in SNU-719 and NCC24 regardless of the MSI status in vitro and in vivo.

conclusionsOur findings suggest that EBV-positivity and MSI-high status are mutually exclusive due to the immediate disadvantage in tumor stemness when MLH1 is silenced, whereas the establishment of MSI-high status in EBV-positive GCs required a longer period.

Indexed as

Microsatellite InstabilityCell Transformation, NeoplasticHerpesvirus 4, HumanHumansStomach NeoplasmsDNA methylationEBVGastric cancerMSITumor stemness

Identifiers

PMID33386473
OpenAlexW3116159364

What OpenQuestion holds

Textmetadata
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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.