Evidence map›Paper›PMID 38902235›Full record

ArticleCell death & disease2024

ALKBH4 impedes 5-FU Sensitivity through suppressing GSDME induced pyroptosis in gastric cancer.

Xin Jiang, Zhiman Zhu, Lina Ding, Wenqi Du, Dongsheng Pei

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Targeting the OXNAD1-PTGS2 axis with resveratrol overcomes ferroptosis Inhibition and reverses 5-FU resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Article
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
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  15. Review
  16. Article
  17. Review
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  19. Review
  20. Cell cycle (Georgetown, Tex.)
    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

5 authors.

Xin Jiang *Department of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Zhiman Zhu *Department of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Lina Ding *Department of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China.
Wenqi DuDepartment of Human Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China. wqdu@xzhmu.edu.cn.
Dongsheng PeiDepartment of Pathology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, China. dspei@xzhmu.edu.cn.ORCID 0000-0002-8053-3741

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

5-Fluorouracil (5-FU) is the primary treatment option for advanced gastric cancer. However, the current challenge lies in the absence of validated biomarkers to accurately predict the efficacy and sensitivity of 5-FU in individual patients. It has been confirmed that 5-FU can regulate tumor progression by promoting gasdermin E (GSDME, encoded by DFNA5) cleavage to induce pyroptosis. Lysine demethylase ALKBH4 has been shown to be upregulated in a variety of tumors to promote tumor progression. However, its role in gastric cancer is not clear. In this study, we observed a significant upregulation of ALKBH4 expression in gastric cancer tissues compared to adjacent normal tissues, indicating its potential as a predictor for the poor prognosis of gastric cancer patients. On the contrary, GSDME exhibits low expression levels in gastric cancer and demonstrates a negative correlation with poor prognosis among patients diagnosed with gastric cancer. In addition, we also found that high expression of ALKBH4 can inhibit pyroptosis and promote the proliferation of gastric cancer cells. Mechanistically, ALKBH4 inhibits GSDME activation at the transcriptional level by inhibiting H3K4me3 histone modification in the GSDME promoter region, thereby reducing the sensitivity of gastric cancer cells to 5-FU treatment. These findings provide further insight into the regulatory mechanisms of ALKBH4 in the progression of gastric cancer and underscore its potential as a prognostic marker for predicting the sensitivity of gastric cancer cells to 5-FU treatment.

Indexed as

FluorouracilPyroptosisStomach NeoplasmsAnimalsCell Line, TumorCell ProliferationDrug Resistance, NeoplasmFemaleGasderminsGene Expression Regulation, NeoplasticHistonesHumansMaleMiceMice, NudePrognosisFluorouracilGasderminsGSDME protein, humanHistones

Identifiers

PMID38902235
PMCPMC11189908

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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.