Evidence map›Paper›PMID 29343747›Full record

ArticleScientific reports2018

Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells.

Masamitsu Konno, Hidetoshi Matsui, Jun Koseki, Ayumu Asai, Yoshihiro Kano, Koichi Kawamoto, Naohiro Nishida, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

13 authors.

Masamitsu KonnoDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Hidetoshi MatsuiFaculty of Data Science, Shiga University, Shiga, 522-8522, Japan.ORCID http://orcid.org/0000-0002-6286-5072
Jun KosekiDepartment of Medical Data Science, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Ayumu AsaiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Yoshihiro KanoDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Koichi KawamotoDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Naohiro NishidaDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Daisuke SakaiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Toshihiro KudoDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Taroh SatohDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan.
Yuichiro DokiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan. ydoki@gesurg.med.osaka-u.ac.jp.
Masaki MoriDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan. mmori@gesurg.med.osaka-u.ac.jp.
Hideshi IshiiDepartment of Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, 565-0871, Japan. hishii@gesurg.med.osaka-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We investigated the relationship between methylomic [5-methylation on deoxycytosine to form 5-methylcytosine (5mC)] and transcriptomic information in response to chemotherapeutic 5-fluorouracil (5-FU) exposure and cisplatin (CDDP) administration using the ornithine decarboxylase (ODC) degron-positive cancer stem cell model of gastrointestinal tumour. The quantification of 5mC methylation revealed various alterations in the size distribution and intensity of genomic loci for each patient. To summarise these alterations, we transformed all large volume data into a smooth function and treated the area as a representative value of 5mC methylation. The present computational approach made the methylomic data more accessible to each transcriptional unit and allowed to identify candidate genes, including the tumour necrosis factor receptor-associated factor 4 (TRAF4), as novel therapeutic targets with a strong response to anti-tumour agents, such as 5-FU and CDDP, and whose significance has been confirmed in a mouse model in vivo. The present study showed that 5mC methylation levels are inversely correlated with gene expression in a chemotherapy-resistant stem cell model of gastrointestinal cancer. This mathematical method can be used to simultaneously quantify and identify chemoresistant potential targets in gastrointestinal cancer stem cells.

Indexed as

5-MethylcytosineAnimalsAntineoplastic AgentsCell Line, TumorCisplatinDNA MethylationDrug Resistance, NeoplasmFemaleFluorouracilGastrointestinal NeoplasmsHumansMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsTranscriptome5-MethylcytosineAntineoplastic AgentsCisplatinFluorouracil

Identifiers

PMID29343747
PMCPMC5772492

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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.