Evidence map›Paper›PMID 25804630›Full record

ArticleGut2016

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis.

Hui Ling, Karen Pickard, Cristina Ivan, Claudio Isella, Mariko Ikuo, Richard Mitter, Riccardo Spizzo, Marc Bullock, Cornelia Braicu, Valentina Pileczki and 30 more

Registry-linked trialOpen access · greenAbstract readMulticenter Study
In one paragraph

Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03309722 (Molecular Pathology of Colorectal Cancer), which is not on this map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
7.6field-weighted citation impact, top 2% 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.

NCT03309722 unknown statusnot on this map

Molecular Pathology of Colorectal Cancer: Investigating the Role of Novel Molecular Profiles, microRNA's, and Their Targets in Colorectal Cancer

TypeobservationalSponsorUniversity of SouthamptonRan2008 to 2025Enrolled1,000ConditionsColorectal CancerArmsbiomarker study
3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 131 citations in OpenAlex.

  1. Review
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  7. Review
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  9. Article
  10. MicroRNA-452: a double-edged sword in multiple human cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  11. Article
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  13. Review
  14. Aging · 2022
    Article
  15. Article
  16. Review
  17. Review
  18. Review
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  20. Article

31 more citing papers are in PubMed but not listed here.

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

40 authors at 14 institutions in 7 countries.

Hui Ling *Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Karen Pickard *Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK.
Cristina Ivan *Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Claudio IsellaUniversity of Torino, Department of Oncology, Torino, Italy.
Mariko IkuoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Richard MitterBioinformatics Unit, London Research Institute, Cancer Research UK, London, UK.
Riccardo SpizzoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Marc BullockDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cornelia BraicuDepartment of Functional Genomics, The Oncology Institute, Cluj-Napoca, Romania.
Valentina PileczkiDepartment of Functional Genomics, The Oncology Institute, Cluj-Napoca, Romania.
Kimberly VincentDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Martin PichlerDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Verena StiegelbauerDivision of Oncology, Medical University of Graz, Austria.
Gerald HoeflerInstitute of Pathology, Medical University of Graz, Austria.
Maria I AlmeidaDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Annie HsiaoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xinna ZhangCenter for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John PrimroseCancer Research UK Centre, University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK.
Graham PackhamCancer Research UK Centre, University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK.
Kevin LiuDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Krishna BojjaDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Roberta GafàSection of Pathology and Molecular Diagnostics, University of Ferrara, Ferrara, Italy.
Lianchun XiaoDivision of Quantitative Science, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Simona RossiDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jian H SongDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ivan VanniniIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) s.r.l., IRCCS, Gene Therapy Unit, Meldola (FC), Italy.
Francesca FaniniIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) s.r.l., IRCCS, Gene Therapy Unit, Meldola (FC), Italy.
Scott KopetzDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Patrick Zweidler-McKayDepartment of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xuemei WangDivision of Quantitative Science, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Calin IonescuSurgical Clinic 1, Cluj County Hospital, Romania.
Alexandru IrimieDepartment of Surgical and Gynecology Oncology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
Muller FabbriDepartments of Pediatrics, and Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, The Saban Research Institute, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Giovanni LanzaSection of Pathology and Molecular Diagnostics, University of Ferrara, Ferrara, Italy.
Stanley R HamiltonDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ioana Berindan-NeagoeDepartment of Functional Genomics, The Oncology Institute, Cluj-Napoca, Romania.
Enzo MedicoUniversity of Torino, Department of Oncology, Torino, Italy.
Alex Mirnezami *Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Somers Cancer Research Building, Southampton University Hospital NHS Trust, Tremona road, Southampton, SO16 6YD, UK.
George A Calin *Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Milena S Nicoloso *Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USCancer Research UK · GBInstitute of Oncology Prof. Dr. Ion Chiricuta · ROCentro di Riferimento Oncologico · ITMedical University of Graz · ATUniversity Hospital Southampton NHS Foundation Trust · GBUniversity of Ferrara · ITUniversity of Turin · ITChildren's Hospital of Los Angeles · USIstituti di Ricovero e Cura a Carattere Scientifico · ITIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori · ITIuliu Hațieganu University of Medicine and Pharmacy · ROSpitalul Clinic CF Cluj-Napoca · ROThe University of Tokyo · JP

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2M
Targeting the p53 pathway for reversal of oral premalignancyP50CA097007 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MYERS, JEFFREY NICHOLAS · 2002 to 2012
$26.1M
UT M.D. Anderson Cancer Center SPORE in MelanomaP50CA093459 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GRIMM, ELIZABETH A · 2004 to 2014
$23.7M
Modulation of Microglia and T Cell Interactions in Malignant GliomaR01CA120813 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HEIMBERGER, AMY BETH, RAO, GANESH · 2007 to 2025
$4.7M
Center for Clinical and Translational Sciences (CCTS)KL2TR000370 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$4.3M
Protein-coding and non-coding RNA biomarkers for early detection of CLLR01CA182905 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABRUZZO, LYNNE V., CALIN, GEORGE A. · 2014 to 2018
$2.9M
Novel extra cellular RNA-based combinatorial RNA inhibition therapyUH2TR000943 · NCATS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., LOPEZ-BERESTEIN, GABRIEL · 2013 to 2014
$1.1M
Medical Research Council MR/K000799/1NCATS NIH HHS KL2 TR000370NCATS NIH HHS UH2 TR000943NCI NIH HHS P30 CA014089NCI NIH HHS P50 CA093459NCI NIH HHS P50 CA097007NCI NIH HHS P50 CA127001NCI NIH HHS R01 CA120813NCI NIH HHS R01 CA182905
6 · The paper itself

Abstract

objectiveMicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis.

designWe performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression.

resultsMiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175).

conclusionsMiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC.

Indexed as

AdenocarcinomaAdultAgedAged, 80 and overAnimalsAustriaBiomarkers, TumorColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansIn Vitro TechniquesItalyKaplan-Meier EstimateMaleMiceBiomarkers, TumorMicroRNAsCOLORECTAL CANCERLIVER METASTASESMICROSATELLITE INSTABILITYMOLECULAR GENETICSRNA EXPRESSION

Identifiers

PMID25804630
PMCPMC4581915
OpenAlexW2151034879

What OpenQuestion holds

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Registered trials

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.