Evidence map›Paper›PMID 26606261›Full record

ArticlePloS one2015

MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma.

Sameer A Dhayat, Wolf Arif Mardin, Jochen Seggewiß, Anda Jana Ströse, Christiane Matuszcak, Richard Hummel, Norbert Senninger, Sören Torge Mees, Jörg Haier

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  5. Review
  6. Review
  7. Impact of Hypoxia-Induced miR-210 on Pancreatic Cancer.Current issues in molecular biology · 2023
    Review
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  9. Article
  10. Article
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  16. Article
  17. Influence ofCancers · 2021
    Article
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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

9 authors at 1 institution in 1 country.

Sameer A DhayatDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Wolf Arif MardinDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Jochen SeggewißIntegrated Functional Genomics, Interdisciplinary Center for Clinical Research, Medical Faculty of the University of Muenster, Muenster, Germany.
Anda Jana StröseComprehensive Cancer Center Muenster, University Hospital Muenster, Muenster, Germany.
Christiane MatuszcakDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Richard HummelDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Norbert SenningerDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Sören Torge MeesDepartment of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
Jörg HaierComprehensive Cancer Center Muenster, University Hospital Muenster, Muenster, Germany.
University Hospital Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNo reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern.

methodsGemcitabine-resistant variants of two mutant p53 human PDAC cell lines were established. Survival rates were analyzed by cytotoxicity and apoptosis assays. Expression of 1733 human miRs was investigated by microarray and validated by qRT-PCR. After in-silico analysis of specific target genes and proteins of dysregulated miRs, expression of MRP-1, Bcl-2, mutant p53, and CDK1 was quantified by Western blot.

resultsBoth established PDAC clones showed a significant resistance to gemcitabine (p<0.02) with low apoptosis rate (p<0.001) vs. parental cells. MiR-screening revealed significantly upregulated (miR-21, miR-99a, miR-100, miR-125b, miR-138, miR-210) and downregulated miRs (miR-31*, miR-330, miR-378) in chemoresistant PDAC (p<0.05). Bioinformatic analysis suggested involvement of these miRs in pathways controlling cell death and cycle. MRP-1 (p<0.02) and Bcl-2 (p<0.003) were significantly overexpressed in both resistant cell clones and mutant p53 (p = 0.023) in one clone.

conclusionConsistent miR expression profiles, in part regulated by mutant TP53 gene, were identified in gemcitabine-resistant PDAC with significant MRP-1 and Bcl-2 overexpression. These results provide a basis for further elucidation of chemoresistance mechanisms and therapeutic approaches to overcome chemoresistance in PDAC.

Indexed as

Genes, p53MutationAntimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalCell Line, TumorCluster AnalysisComputational BiologyDeoxycytidineDrug Resistance, NeoplasmGemcitabineGene Expression ProfilingHumansMicroRNAsPancreatic NeoplasmsReproducibility of ResultsRNA InterferenceAntimetabolites, AntineoplasticDeoxycytidineGemcitabineMicroRNAsRNA, Messenger

Identifiers

PMID26606261
PMCPMC4659591
OpenAlexW2179483056

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Registered trials

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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.