Evidence map›Paper›PMID 26857392›Full record

ArticleJournal of the National Cancer Institute2016

Relevance of Sp Binding Site Polymorphism in WWOX for Treatment Outcome in Pancreatic Cancer.

Markus A Schirmer, Claudia M Lüske, Sebastian Roppel, Alexander Schaudinn, Christian Zimmer, Ruben Pflüger, Martin Haubrock, Jacobe Rapp, Cenap Güngör, Maximilian Bockhorn and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

21 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. BIK polymorphism and proteasome regulation unveil host risk factor for severe influenza.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Review
  6. Review
  7. International journal of medical sciences · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Involvement of FGFR4 Gene Variants on the Clinicopathological Severity in Urothelial Cell Carcinoma.International journal of environmental research and public health · 2019
    Article
  12. Impact of Long Non-Coding RNAJournal of clinical medicine · 2019
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 1 country.

Markus A SchirmerAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Claudia M LüskeAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Sebastian RoppelAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Alexander SchaudinnAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Christian ZimmerAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Ruben PflügerAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Martin HaubrockAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Jacobe RappAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Cenap GüngörAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Maximilian BockhornAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Thilo HackertAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Thomas HankAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Oliver StrobelAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Jens WernerAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Jakob R IzbickiAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Steven A JohnsenAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Jochen GaedckeAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Jürgen BrockmöllerAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
B Michael GhadimiAffiliations of authors:Institute of Clinical Pharmacology (MAS, CML, SR, AS, CZ, RP, JB), Institute of Bioinformatics (MH), Clinic of General and Visceral Surgery (CML, SR, JR, SAJ, JG, BMG), and Clinic of Radiotherapy and Radiation Oncology (MAS), University Medical Center Göttingen , Göttingen , Germany ; Department of General, Visceral, and Thoracic Surgery, University Hospital Hamburg-Eppendorf , Hamburg , Germany (CG, MB, JRI); Department of General, Visceral, and Transplantation Surgery, University of Heidelberg , Heidelberg , Germany (THac, THan, OS, JW).
Universitätsmedizin Göttingen · DEUniversity of Göttingen · DEUniversity Medical Center Hamburg-Eppendorf · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects.

methodsThis study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy. The primary outcome was the relationship between germline polymorphisms and OS. Functional assays addressed pharmacological dose-response effects in lymphoblastoid cell lines (LCLs) and pancreatic cancer cell lines (including upon RNAi), gene expression analyses, and allele-specific transcription factor binding. All statistical tests were two-sided.

resultsThe A allele (26% in Caucasians) at SNP rs11644322 in the putative tumor suppressor gene WWOX conferred worse prognosis. Median OS was 14 months (95% confidence interval [CI] = 12 to 15 months), 13 months (95% CI = 11 to 15 months), and nine months (95% CI = 7 to 12 months) for the GG, GA, and AA genotypes, respectively (P trend < .001 for trend in univariate log-rank assuming a codominant mode of inheritance; advanced disease subgroup P trend < .001). Mean OS was 25 months (95% CI = 21 to 29 months), 19 months (95% CI = 15 to 22 months), and 13 months (95% CI = 10 to 16 months), respectively. This effect held true after adjustment for age, performance status according to Eastern Cooperative Oncology Group classification, TNM, grading, and resection status and was comparable with the strongest established prognostic factors in multivariable analysis. Consistently, reduced responsiveness to gemcitabine, but not 5-fluorouracil, along with lower WWOX expression was demonstrated in LCLs harboring the AA genotype. Likewise, RNAi-mediated WWOX knockdown in pancreatic cancer cells confirmed differential cytostatic drug sensitivity. In electrophoretic mobility shift assays, the A allele exhibited weaker binding of Sp family members Sp1/Sp3.

conclusionsWWOX rs11644322 represents a major predictive factor in gemcitabine-treated pancreatic cancer. Decreased WWOX expression may interfere with gemcitabine sensitivity, and allele-specific binding at rs11644332 might be a causative molecular mechanism behind the observed clinical associations.

Indexed as

Polymorphism, Single NucleotideAdenocarcinomaAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Pancreatic DuctalDeoxycytidineDose-Response Relationship, DrugDrug Administration ScheduleDrug Resistance, NeoplasmElectrophoretic Mobility Shift AssayFemaleGemcitabineGene Expression Regulation, NeoplasticGene Knockdown TechniquesBiomarkers, TumorDeoxycytidineGemcitabineOxidoreductasesSp Transcription FactorsTumor Suppressor ProteinsWW Domain-Containing OxidoreductaseWWOX protein, human

Identifiers

PMID26857392
PMCPMC4859408
OpenAlexW2268371169

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.