Evidence map›Paper›PMID 21949851›Full record

ArticlePloS one2011

TGFBR2 and BAX mononucleotide tract mutations, microsatellite instability, and prognosis in 1072 colorectal cancers.

Kaori Shima, Teppei Morikawa, Mai Yamauchi, Aya Kuchiba, Yu Imamura, Xiaoyun Liao, Jeffrey A Meyerhardt, Charles S Fuchs, Shuji Ogino

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

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
3.6field-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

26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis.Annals of oncology : official journal of the European Society for Medical Oncology · 2016
    Pooled it
  3. Review
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  13. Advantage ofOncotarget · 2018
    Article
  14. Article
  15. Microsatellite Instability in Mouse Models of Colorectal Cancer.Canadian journal of gastroenterology & hepatology · 2018
    Article
  16. TGF-β Family Signaling in Tumor Suppression and Cancer Progression.Cold Spring Harbor perspectives in biology · 2017
    Review
  17. Article
  18. Article
  19. Article
  20. 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.

Kaori ShimaDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
Teppei Morikawa
Mai Yamauchi
Aya Kuchiba
Yu Imamura
Xiaoyun Liao
Jeffrey A Meyerhardt
Charles S Fuchs
Shuji Ogino
Harvard University · USDana-Farber Cancer Institute · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI GIOVANNUCCI, EDWARD · 1991 to 2009
$41.8M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2M
Epigenetic Events and Colorectal Cancer EpidemiologyR01CA151993 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2010 to 2014
$2.6M
The Influence of Diet and Lifestyle on Patients with Advanced Colorectal CancerR01CA149222 · NCI · DANA-FARBER CANCER INST · PI MEYERHARDT, JEFFREY A · 2010 to 2014
$2.4M
Molecular Epidemiology of Colorectal CancerK07CA122826 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2007 to 2010
$634k
NCI NIH HHS K07 CA122826NCI NIH HHS K07CA122826NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P01CA55075NCI NIH HHS P01CA87969NCI NIH HHS P50 CA127003NCI NIH HHS P50CA127003NCI NIH HHS R01 CA149222NCI NIH HHS R01 CA151993NCI NIH HHS R01CA151993
6 · The paper itself

Abstract

backgroundMononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high) colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-β, TGF-β) signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer as a prognostic biomarker remains uncertain. METHODOLOGY/PRINCIPAL

findingsWe utilized a database of 1072 rectal and colon cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study). Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusted for clinical, pathological and molecular features including the CpG island methylator phenotype (CIMP), LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072) of all colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74% (117/159) and 30% (48/158) of MSI-high tumors, respectively. In Kaplan-Meier analysis as well as univariate and multivariate Cox regression analyses, compared to microsatellite stable (MSS)/MSI-low cases, MSI-high cases were associated with superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence interval (CI), 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI-high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66; p = 0.0011].

conclusionsTGFBR2 or BAX mononucleotide mutations are not associated with the patient survival outcome in MSI-high colorectal cancer. Our data do not support those mutations as prognostic biomarkers (beyond MSI) in colorectal carcinoma.

Indexed as

Microsatellite InstabilityAgedbcl-2-Associated X ProteinClass I Phosphatidylinositol 3-KinasesCohort StudiesColorectal NeoplasmsCpG IslandsDNA MethylationDNA, NeoplasmFemaleFollow-Up StudiesHumansLong Interspersed Nucleotide ElementsMaleMutationNeoplasm GradingBAX protein, humanbcl-2-Associated X ProteinBRAF protein, humanClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmKRAS protein, humanPhosphatidylinositol 3-KinasesPIK3CA protein, humanProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type II

Identifiers

PMID21949851
PMCPMC3176811
OpenAlexW2093204178

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.