Evidence map›Paper›PMID 39067134›Full record

ArticleEBioMedicine2024

A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.

Hui Yang, Xinzhi Wang, Adrián Blanco-Gómez, Li He, Natalia García-Sancha, Roberto Corchado-Cobos, Manuel Jesús Pérez-Baena, Alejandro Jiménez-Navas, Pin Wang, Jamie L Inman and 6 more

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Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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.

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

9 citing papers in PubMed.

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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

16 authors.

Hui YangBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Xinzhi WangBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Adrián Blanco-GómezInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain.
Li HeBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430079, China.
Natalia García-SanchaInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain.
Roberto Corchado-CobosInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain.
Manuel Jesús Pérez-BaenaInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain.
Alejandro Jiménez-NavasInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain.
Pin WangBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
Jamie L InmanBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Antoine M SnijdersBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
David W ThreadgillDepartment of Nutrition, Texas A&M University, College Station, TX, 77843, USA; Department of Molecular and Cellular Medicine and Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX, 77843, USA.
Allan BalmainHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94158, USA.
Hang ChangBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. Electronic address: hchang@lbl.gov.
Jesus Perez-LosadaInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, 37007, Spain; Instituto de Investigación Biosanitaria de Salamanca (IBSAL), Salamanca, 37007, Spain. Electronic address: jperezlosada@usal.es.
Jian-Hua MaoBiological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. Electronic address: JHMao@lbl.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDeeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis.

methods732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice.

findingsDistinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment.

interpretationOur investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC.

fundingThe U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the "European Union Next Generation EU/PRTR," the Regional Government of Castile and León (CSI144P20), European Union.

Indexed as

Collaborative Cross MiceErb-b2 Receptor Tyrosine KinasesGenetic Predisposition to DiseasePolymorphism, Single NucleotideAnimalsBiomarkers, TumorBreast NeoplasmsDisease Models, AnimalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansMiceNeoplasm MetastasisTranscriptomeBiomarkers, TumorERBB2 protein, humanErbb2 protein, mouseErb-b2 Receptor Tyrosine KinasesBreast cancerCollaborative cross miceGene signaturePrognosisTreatment response predictionTumour susceptibility

Identifiers

PMID39067134
PMCPMC11338061

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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.