Evidence map›Paper›PMID 25236463›Full record

ArticleBioinformatics (Oxford, England)2015

Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis.

Timo Itzel, Peter Scholz, Thorsten Maass, Markus Krupp, Jens U Marquardt, Susanne Strand, Diana Becker, Frank Staib, Harald Binder, Stephanie Roessler and 5 more

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

Article in Bioinformatics (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

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  16. The role of theAnnals of translational medicine · 2020
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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

15 authors at 6 institutions in 2 countries.

Timo ItzelDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Peter ScholzDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Thorsten MaassDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Markus KruppDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Jens U MarquardtDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Susanne StrandDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Diana BeckerDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Frank StaibDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Harald BinderDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Stephanie RoesslerDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Xin Wei WangDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Snorri ThorgeirssonDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Martina MüllerDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Peter R GalleDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
Andreas TeufelDepartment of Medicine I, University of Regensburg, 93053, Regensburg, Department of Medicine I, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131, Mainz, Department of Pathology, University of Heidelberg, 69120, Germany and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892 MD, USA.
National Cancer Institute · USUniversity Hospital Heidelberg · DEHeidelberg University · DEJohannes Gutenberg University Mainz · DEUniversity Medical Center · USUniversity of Regensburg · DE

Funding

Strategies for improving early detection, diagnosis and treatment of liver cancerZIABC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$18.1M
Molecular signatures for liver cancer diagnosis and treatment stratificationZ01BC010313 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 1999 to 2008
$1.8M
Intramural NIH HHSNCI NIH HHS Z01 BC 010313
6 · The paper itself

Abstract

motivationCo-regulated genes are not identified in traditional microarray analyses, but may theoretically be closely functionally linked [guilt-by-association (GBA), guilt-by-profiling]. Thus, bioinformatics procedures for guilt-by-profiling/association analysis have yet to be applied to large-scale cancer biology. We analyzed 2158 full cancer transcriptomes from 163 diverse cancer entities in regard of their similarity of gene expression, using Pearson's correlation coefficient (CC). Subsequently, 428 highly co-regulated genes (|CC| ≥ 0.8) were clustered unsupervised to obtain small co-regulated networks. A major subnetwork containing 61 closely co-regulated genes showed highly significant enrichment of cancer bio-functions. All genes except kinesin family member 18B (KIF18B) and cell division cycle associated 3 (CDCA3) were of confirmed relevance for tumor biology. Therefore, we independently analyzed their differential regulation in multiple tumors and found severe deregulation in liver, breast, lung, ovarian and kidney cancers, thus proving our GBA hypothesis. Overexpression of KIF18B and CDCA3 in hepatoma cells and subsequent microarray analysis revealed significant deregulation of central cell cycle regulatory genes. Consistently, RT-PCR and proliferation assay confirmed the role of both genes in cell cycle progression. Finally, the prognostic significance of the identified KIF18B- and CDCA3-dependent predictors (P = 0.01, P = 0.04) was demonstrated in three independent HCC cohorts and several other tumors. In summary, we proved the efficacy of large-scale guilt-by-profiling/association strategies in oncology. We identified two novel oncogenes and functionally characterized them. The strong prognostic importance of downstream predictors for HCC and many other tumors indicates the clinical relevance of our findings. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Indexed as

Gene Expression Regulation, NeoplasticBiomarkers, TumorBlotting, WesternCarcinogenesisCarcinoma, HepatocellularCell CycleCell Cycle ProteinsCell ProliferationComputational BiologyDisease ProgressionFlow CytometryGene Expression ProfilingHumansKinesinsLiver NeoplasmsNeoplasmsBiomarkers, TumorCDCA3 protein, humanCell Cycle ProteinsKIF18B protein, humanKinesins

Identifiers

PMID25236463
PMCPMC4287940
OpenAlexW2083892997

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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.