Evidence map›Paper›PMID 29335598›Full record

ArticleScientific reports2018

Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.

Eric R Gamazon, Matthew R Trendowski, Yujia Wen, Claudia Wing, Shannon M Delaney, Won Huh, Shan Wong, Nancy J Cox, M Eileen Dolan

Open access · goldAbstract 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 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. 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

9 authors at 2 institutions in 1 country.

Eric R GamazonSection of Genetic Medicine, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA. egamazon@uchicago.edu.ORCID http://orcid.org/0000-0003-4204-8734
Matthew R TrendowskiSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Yujia WenSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Claudia WingSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Shannon M DelaneySection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Won HuhSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Shan WongSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
Nancy J CoxSection of Genetic Medicine, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA.
M Eileen DolanSection of Hematology/Oncology, Department of Medicine, the University of Chicago, Chicago, IL, 60637, USA. edolan@medicine.bsd.uchicago.edu.ORCID http://orcid.org/0000-0003-1613-097X
University of Chicago · USVanderbilt University · US

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI RATAIN, MARK J · 2000 to 2014
$39.0M
Genetic Susceptibility and Biomarkers of Platinum-related ToxicitiesR01CA157823 · NCI · UNIVERSITY OF ROCHESTER · PI TRAVIS, LOIS B. · 2012 to 2025
$11.2M
Harnessing GTEx to Create Transcriptome Knowledge and Inform Disease BiologyR01MH101820 · NIMH · UNIVERSITY OF CHICAGO · PI COX, NANCY J, NICOLAE, DAN LIVIU · 2013 to 2015
$2.3M
Genetic determinants associated with pemetrexed response and toxicityR01CA136765 · NCI · UNIVERSITY OF CHICAGO · PI DOLAN, MARY EILEEN · 2009 to 2013
$1.6M
Using the Transcriptome for SNP and Gene AnnotationR01MH090937 · NIMH · UNIVERSITY OF CHICAGO · PI COX, NANCY J, NICOLAE, DAN LIVIU · 2010 to 2012
$825k
NCI NIH HHS P30 CA014599NCI NIH HHS R01 CA136765NCI NIH HHS R01 CA157823NIGMS NIH HHS U01 GM061393NIMH NIH HHS R01 MH090937NIMH NIH HHS R01 MH101820
6 · The paper itself

Abstract

Pemetrexed is indicated for non-small cell lung carcinoma and mesothelioma, but often has limited efficacy due to drug resistance. To probe the molecular mechanisms underlying chemotherapeutic response, we performed mRNA and microRNA (miRNA) expression profiling of pemetrexed treated and untreated lymphoblastoid cell lines (LCLs) and applied a hierarchical Bayesian method. We identified genetic variation associated with gene expression in human lung tissue for the most significant differentially expressed genes (Benjamini-Hochberg [BH] adjusted p < 0.05) using the Genotype-Tissue Expression data and found evidence for their clinical relevance using integrated molecular profiling and lung adenocarcinoma survival data from The Cancer Genome Atlas project. We identified 39 miRNAs with significant differential expression (BH adjusted p < 0.05) in LCLs. We developed a gene expression based imputation model of drug sensitivity, quantified its prediction performance, and found a significant correlation of the imputed phenotype generated from expression data with survival time in lung adenocarcinoma patients. Differentially expressed genes (MTHFD2 and SUFU) that are putative targets of differentially expressed miRNAs also showed differential perturbation in A549 fusion lung tumor cells with further replication in A549 cells. Our study suggests pemetrexed may be used in combination with agents that target miRNAs to increase its cytotoxicity.

Indexed as

AdenocarcinomaAdenocarcinoma of LungAntineoplastic AgentsCell Line, TumorDrug ResistanceEpithelial CellsGene Expression ProfilingGene Expression RegulationHumansLung NeoplasmsLymphocytesMicroRNAsModels, BiologicalPemetrexedAntineoplastic AgentsMicroRNAsPemetrexed

Identifiers

PMID29335598
PMCPMC5768793
OpenAlexW2782694424

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.