Evidence map›Paper›PMID 40259317›Full record

ArticleBMC cancer2025

Associations of blood RNA biomarkers and circulating tumour cells in patients with previously untreated metastatic colorectal cancer.

Manuel Valladares-Ayerbes, Marta Toledano-Fonseca, Begoña Graña, Paula Jimenez-Fonseca, Gema Pulido-Cortijo, Silvia Gil, Javier Sastre, Antonieta Salud, Fernando Rivera, Mercedes Salgado and 8 more

2 registry-linked trialsAbstract read
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

NCT01640405 phase3completednot on this map

Phase III, Randomized Clinical Trial to Evaluate FOLFOX + Bevacizumab Versus FOLFOXIRI + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells.

TypeinterventionalSponsorSpanish Cooperative Group for the Treatment of Digestive Tumours (TTD)Ran2012 to 2018Enrolled350ConditionsMetastatic Colorectal CancerArmsmodified FOLFOX6 + bevacizumab, FOLFOXIRI + Bevacizumab
NCT01640444 phase2completednot on this map

Randomized Phase II Study to Explore the Influence of BRAF and PIK3K Status on the Efficacy of FOLFIRI Plus Bevacizumab or Cetuximab, as First Line Therapy of Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells

TypeinterventionalSponsorSpanish Cooperative Group for the Treatment of Digestive Tumours (TTD)Ran2012 to 2018Enrolled240ConditionsColorectal Cancer MetastaticArmsFOLFIRI + bevacizumab, FOLFIRI + cetuximab
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

18 authors.

Manuel Valladares-AyerbesDepartment of Medical Oncology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina (IBIS), Seville, Spain. mvalaye@icloud.com.ORCID http://orcid.org/0000-0002-7950-9584
Marta Toledano-FonsecaDepartment of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
Begoña GrañaDepartment of Medical Oncology, Instituto de Investigación Biomédica (INIBIC), Hospital Universitario de A Coruña, A Coruña, Spain.
Paula Jimenez-FonsecaDepartment of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain.
Gema Pulido-CortijoDepartment of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
Silvia GilDepartment of Medical Oncology, Hospital Regional Universitario de Málaga, Málaga, Spain.
Javier SastreDepartment of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación (IdISSC), Universidad Complutense, Madrid, Spain.
Antonieta SaludDepartment of Medical Oncology, Hospital Universitario Arnau de Vilanova, Lleida, Spain.
Fernando RiveraDepartment of Medical Oncology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Mercedes SalgadoDepartment of Medical Oncology, Complejo Hospitalario Universitario de Ourense, Ourense, Spain.
Pilar García-AlfonsoDepartment of Medical Oncology, Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain.
Rafael López LópezDepartment of Medical Oncology and Translational Medical Oncology Group, Hospital Clínico Universitario, Instituto de Investigación Sanitaria de Santiago (IDIS), CIBERONC, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Carmen Guillén-PonceDepartment of Medical Oncology, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Antonio Rodríguez-ArizaDepartment of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
Jose Mª VieitezDepartment of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain.
Eduardo Díaz-RubioDepartment of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación (IdISSC), Universidad Complutense, Madrid, Spain.
Enrique ArandaDepartment of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn patients with metastatic colorectal cancer, analysis of the number of basal circulating tumour cells (bCTCs) has been shown to be a strong prognostic indicator. In this study, we aim to explore the potential associations between whole blood mRNA and microRNA expression profiles and bCTC counts, tumour mutations and prognosis in untreated metastatic colorectal cancer patients.

methodsA total of 151 patients previously screened for inclusion in two clinical trials (VISNÚ1 and VISNÚ2) were enrolled in this study. Real-time quantitative PCR (qPCR) analyses were performed to determine the whole blood expression of selected RNAs (mRNAs and microRNAs) involved in the metastatic process. The CellSearch system was used to enumerate circulating tumour cells. The primary objective was to correlate RNA expression with the number of bCTCs, while the secondary objectives were to investigate the relationship between the levels of circulating RNA biomarkers in whole blood and the clinical, pathological, and molecular characteristics and prognosis of patients with metastatic colorectal cancer.

resultsbCTC count was significantly associated with AGR2 mRNA in the entire cohort of 151 patients. AGR2, ADAR1 and LGR5 were associated with the number of bCTC, both in the subgroup with bCTC ≥ 3 and in the subgroup with native RAS/BRAF/PIK3 CA tumours. In patients with RAS/BRAF/PIK3 CA mutations no correlations with bCTC were detected, but an upregulation of miR-224-5p and the stemness marker LGR5 and a downregulation of immune regulatory CD274 were found. Lower levels of miR-106a-5p/miR-26a-5p were associated with shorter overall survival, with independent statistical significance in the multivariate analysis.

conclusionsA correlation was identified between the levels of a subset of whole blood RNAs, including AGR2, ADAR1, and LGR5, and the number of bCTC and RAS/BRAF/PIK3 CA mutational status. Furthermore, another set of whole blood RNAs, specifically miR-106a-5p and miR-26a-5p, was found to be associated with poor prognosis. This may be helpful for risk stratification.

trial registrationClinical Trials Gov. NCT01640405 and NCT01640444. Registered on 13 June 2012. https://clinicaltrials.gov/ .

Indexed as

Biomarkers, TumorColorectal NeoplasmsMicroRNAsNeoplastic Cells, CirculatingRNA, MessengerAdultAgedClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMulticenter Studies as TopicMutationBiomarkers, TumorBRAF protein, humanMicroRNAsProto-Oncogene Proteins B-rafRNA, MessengerCirculating tumour cellsLiquid biopsyMetastatic colorectal cancerPrognosisRNA biomarkers

Identifiers

PMID40259317
PMCPMC12013160

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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.