Evidence map›Paper›PMID 24555920›Full record

ArticleBMC cancer2014

A study of gene expression markers for predictive significance for bevacizumab benefit in patients with metastatic colon cancer: a translational research study of the Hellenic Cooperative Oncology Group (HeCOG).

George Pentheroudakis, Vassiliki Kotoula, Elena Fountzilas, George Kouvatseas, George Basdanis, Ioannis Xanthakis, Thomas Makatsoris, Elpida Charalambous, Demetris Papamichael, Epaminontas Samantas and 7 more

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

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04863768 (Molecular Profiling of Colorectal Cancer), which is not on this map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 16% 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.

NCT04863768 unknown statusnot on this map

Molecular Profiling of Colorectal Cancer: A Translational Research Study With a Next Generation Sequencing Panel.

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan2006 to 2022Enrolled300ConditionsColorectal Cancer, Colon Cancer, Colon AdenocarcinomaArmsGene panel
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 35 citations in OpenAlex.

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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

17 authors at 10 institutions in 2 countries.

George PentheroudakisDepartment of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. gpenther@otenet.gr.
Vassiliki Kotoula
Elena Fountzilas
George Kouvatseas
George Basdanis
Ioannis Xanthakis
Thomas Makatsoris
Elpida Charalambous
Demetris Papamichael
Epaminontas Samantas
Pavlos Papakostas
Dimitrios Bafaloukos
Evangelia Razis
Christos Christodoulou
Ioannis Varthalitis
Nicholas Pavlidis
George Fountzilas
Aristotle University of Thessaloniki · GRMetropolitan Hospital · GRUniversity Hospital of Ioannina · GRBank of Cyprus Oncology Center · CYChania General Hospital ”St. George” · GRHippocration General Hospital · GRHospital Agioi Anargyroi · GRHygeia Hospital · GRPapageorgiou General Hospital · GRUniversity of Patras · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking.

methodsWe profiled expession of 24526 genes by means of whole genome 24 K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set). Genes with correlation to 8-month Progression-free status were studied by means of qPCR in two independent colon cancer cohorts: 49 patients treated with bevacizumab + chemotherapy (Bevacizumab qPCR set) and 72 patients treated with chemotherapy only (Control qPCR set). Endpoints were best tumor response before metastasectomy (ORR) and progression-free survival (PFS).

resultsFive genes were significantly correlated to 8-month progression-free status in the Test set: overexpression of KLF12 and downregulation of AGR2, ALDH6A1, MCM5, TFF2. In the two independent datasets, irinotecan- or oxaliplatin-based chemotherapy was administered as first-line treatment and metastasectomies were subsequently applied in 8-14% of patients. No prognostically significant gene classifier encompassing all five genes could be validated in the Bevacizumab or Control qPCR sets. The complex gene expression profile of all-low tumor (ALDH6A1 + TFF2 + MCM5) was strongly associated with ORR in the Bevacizumab qPCR set (ORR 85.7%, p = 0.007), but not in the Control set (ORR 36.4%, p = 0.747). The Odds Ratio for response for the all-low tumor (ALDH6A1 + TFF2 + MCM5) profile versus any other ALDH6A1 + TFF2 + MCM5 profile was 15 (p = 0.018) in the Bevacizumab qPCR set but only 0.72 (p = 0.63) in the Control set. The tumor expression profile of (KLF12-high + TFF2-low) was significantly associated with PFS only in the Bevacizumab qPCR set: bevacizumab-treated patients with (KLF12-high + TFF2-low) tumors had superior PFS (median 14 months, 95% CI 2-21) compared to patients with any other (KLF12 + TFF2) expression profile (median PFS 7 months, 95% CI 5-10, p = 0.021). The Hazard Ratio for disease progression for (KLF12-high + TFF2-low) versus any other KLF12 + TFF2 expression profile was 2.92 (p = 0.03) in the Validation and 1.29 (p = 0.39) in the Control set.

conclusionsOur «three-stage» hypothesis-generating study failed to validate the prognostic significance of a five-gene classifier in mCRC patients. Exploratory analyses suggest two gene signatures that are potentially associated with bevazicumab benefit in patients with advanced colon cancer.

Indexed as

Gene Expression Regulation, NeoplasticAdultAgedAntibodies, Monoclonal, HumanizedBevacizumabBiomarkers, TumorCohort StudiesColonic NeoplasmsFemaleGreeceHumansMaleMedical OncologyMiddle AgedPredictive Value of TestsTranslational Research, BiomedicalAntibodies, Monoclonal, HumanizedBevacizumabBiomarkers, TumorTFF2 protein, humanTrefoil Factor-2

Identifiers

PMID24555920
PMCPMC3933361
OpenAlexW1999928675

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LicenceCC BY
Read underepoch 390

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.