Association of FOSL1 copy number alteration and triple negative breast tumors

Serino, Leandro Tamião Rodrigues; Jucoski, Tayana Schultz; Morais, Stephanie Bath de; Fernandes, Cíntia Callegari Coêlho; Lima, Rubens Silveira de; Úrban, Cícero; Cavalli, Luciane R.; Cavalli, Iglenir João; Ribeiro, Enilze Maria de Souza Fonseca

doi:10.1590/1678-4685-gmb-2017-0267

Cited by 7 publications

(10 citation statements)

References 37 publications

(43 reference statements)

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“…For instance, the neoplastic cells of the advanced TNBC and atypical malignant tumors usually exhibit moderate-to-strong nuclear staining for FOSL1 [90]. At the same time, the differences in FOSL1 levels and copy numbers between HER2-enriched and TNBC are not significant [91][92][93]. The highest FOSL1 expression occurs in metastatic lesions of lymph nodes where it is about 50% higher than non-metastatic tumors.…”

Section: Fosl1 As a Prognostic Toolmentioning

confidence: 99%

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis

Соболев

Хашукоева

Evina

et al. 2022

IJMS

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The transcription factor FOSL1 plays an important role in cell differentiation and tumorigenesis. Primarily, FOSL1 is crucial for the differentiation of several cell lineages, namely adipocytes, chondrocytes, and osteoblasts. In solid tumors, FOSL1 controls the progression of tumor cells through the epithelial–mesenchymal transformation. In this review, we summarize the available data on FOSL1 expression, stabilization, and degradation in the cell. We discuss how FOSL1 is integrated into the intracellular signaling mechanisms and provide a comprehensive analysis of FOSL1 influence on gene expression. We also analyze the pathological changes caused by altered Fosl1 expression in genetically modified mice. In addition, we dedicated a separate section of the review to the role of FOSL1 in human cancer. Primarily, we focus on the FOSL1 expression pattern in solid tumors, FOSL1 importance as a prognostic factor, and FOSL1 perspectives as a molecular target for anticancer therapy.

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Section: Fosl1 As a Prognostic Toolmentioning

confidence: 99%

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis

Соболев

Хашукоева

Evina

et al. 2022

IJMS

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“…For outcome measurement, definitions of OS and RFS were considered as well as whether follow up time was reported. Definitions of OS or RFS were not reported in six studies (20,41,44,(46)(47)(48), as such, for these six studies, plus an additional study (45), it was unclear whether the method of RFS and OS measurement were standard (outcome measurement). Also, for outcome measurement, four studies (20,32,46,48) failed to report follow up time.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis

et al. 2022

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BackgroundUp to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). CCND1 encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. CCND1 amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of CCND1 amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate CCND1 amplification as a prognostic and predictive biomarker in BCa.Materials and MethodsPublications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, in vitro and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, CCND1 amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].ResultsCCND1 amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). CCND1 amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, CCND1 amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.ConclusionWhile a lack of standardised approach for the detection of CCND1 amplification is to be considered as a limitation, CCND1 amplification was found to be prognostic of shorter RFS and OS in BCa. CCND1 amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of CCND1 amplification, CCND1 amplification would have potential as a predictive biomarker in breast cancer patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.

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“…Genome instability-related mutation and copy number variation (CNV) were also identified in TNBC ( Schmitt et al, 2012 ). For instance, germline mutations in BRCA1 , BRCA2 , ATM , PALB2 , RAD51D , and RAD50 disrupted DNA damage repair pathways in TNBC ( Wu et al, 2019 ); FOSL1 had significantly higher CNV gains in TNBC than in other types of breast cancer ( Serino et al, 2019 ); PIK3CA had high mutation frequency and copy number gains and highly ethnic-specific in TNBC ( Jiang et al, 2019 ); somatic mutation and CNV-derived genomic metrics were significantly associated with immune prognostic category in TNBC ( Karn et al, 2017 ). Furthermore, somatic mutations and CNVs were associated with dysregulation of multiple genes in TNBC.…”

Section: Introductionmentioning

confidence: 99%

Genome Instability-Derived Genes Are Novel Prognostic Biomarkers for Triple-Negative Breast Cancer

Guo¹,

Wang²

2021

Front. Cell Dev. Biol.

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BackgroundTriple-negative breast cancer (TNBC) is an aggressive disease. Recent studies have identified genome instability-derived genes for patient outcomes. However, most of the studies mainly focused on only one or a few genome instability-related genes. Prognostic potential and clinical significance of genome instability-associated genes in TNBC have not been well explored.MethodsIn this study, we developed a computational approach to identify TNBC prognostic signature. It consisted of (1) using somatic mutations and copy number variations (CNVs) in TNBC to build a binary matrix and identifying the top and bottom 25% mutated samples, (2) comparing the gene expression between the top and bottom 25% samples to identify genome instability-related genes, and (3) performing univariate Cox proportional hazards regression analysis to identify survival-associated gene signature, and Kaplan–Meier, log-rank test, and multivariate Cox regression analyses to obtain overall survival (OS) information for TNBC outcome prediction.ResultsFrom the identified 111 genome instability-related genes, we extracted a genome instability-derived gene signature (GIGenSig) of 11 genes. Through survival analysis, we were able to classify TNBC cases into high- and low-risk groups by the signature in the training dataset (log-rank test p = 2.66e−04), validated its prognostic performance in the testing (log-rank test p = 2.45e−02) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (log-rank test p = 2.57e−05) datasets, and further validated the predictive power of the signature in five independent datasets.ConclusionThe identified novel signature provides a better understanding of genome instability in TNBC and can be applied as prognostic markers for clinical TNBC management.

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Association of FOSL1 copy number alteration and triple negative breast tumors

Cited by 7 publications

References 37 publications

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis

Prognostic and Predictive Value of CCND1/Cyclin D1 Amplification in Breast Cancer With a Focus on Postmenopausal Patients: A Systematic Review and Meta-Analysis

Genome Instability-Derived Genes Are Novel Prognostic Biomarkers for Triple-Negative Breast Cancer

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