Evidence map›Paper›PMID 28319171›Full record

ArticlePloS one2017

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

Kim E M van Kessel, Harmen J G van de Werken, Irene Lurkin, Angelique C J Ziel-van der Made, Ellen C Zwarthoff, Joost L Boormans

Open access · goldAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. [Molecular tumor board-urothelial cancer].Der Urologe. Ausg. A · 2019
    Review
  3. Article
  4. Article
  5. Article
  6. 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

6 authors at 1 institution in 1 country.

Kim E M van KesselDepartment of Pathology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Harmen J G van de WerkenDepartment of Urology, Cancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Irene LurkinDepartment of Pathology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Angelique C J Ziel-van der MadeDepartment of Pathology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Ellen C ZwarthoffDepartment of Pathology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Joost L BoormansDepartment of Urology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Erasmus MC Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy.

methodsWe studied diagnostic transurethral resection of bladder tumors (dTURBT) of 150 MIBC patients (urothelial carcinoma) who were subsequently treated by radical cystectomy and pelvic lymph node dissection. RNA was isolated and the expression level of the 20 genes was determined on a qRT-PCR platform. Normalized Ct values were used to calculate a risk score to predict the presence of node-positive disease. The Cancer Genome Atlas (TCGA) RNA expression data was analyzed to subsequently validate the results.

resultsIn a univariate regression analysis, none of the 20 genes significantly correlated with node-positive disease. The area under the curve of the risk score calculated by the 20-gene expression signature was 0.54 (95% Confidence Interval: 0.44-0.65) versus 0.67 for the model published by Smith et al. Node-negative patients had a significantly lower tumor grade at TURBT (p = 0.03), a lower pT stage (p<0.01) and less frequent lymphovascular invasion (13% versus 38%, p<0.01) at radical cystectomy than node-positive patients. In addition, in the TCGA data, none of the 20 genes was differentially expressed in node-negative versus node-positive patients.

conclusionsWe conclude that a 20-gene expression signature developed for nodal staging of MIBC at radical cystectomy could not be validated on a qRT-PCR platform in a large cohort of dTURBT specimens.

Indexed as

CystectomyTranscriptomeAdultAgedAged, 80 and overBiomarkers, TumorCarcinomaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisLymph Node ExcisionMaleMiddle AgedMuscle NeoplasmsBiomarkers, Tumor

Identifiers

PMID28319171
PMCPMC5358850
OpenAlexW2603914834

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.