Screening of Prognostic Factors in Early-Onset Breast Cancer

Yu, Zhun; He, Qi; Xu, Guoping

doi:10.1177/1533033819893670

Cited by 13 publications

(17 citation statements)

References 29 publications

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“…High SQLE mRNA expression was significantly associated with a poor prognosis in the ‘all’, lymph node negative, lymph node positive, luminal A subtype and luminal B subtype groups. The present results support the findings of previous studies ( 17 , 18 , 20 – 24 , 26 ) and suggest that high SQLE expression assessed by immunohistochemistry may be associated with a more aggressive phenotype in BC and may be used as a prognostic marker in patients with BC.…”

Section: Discussionsupporting

confidence: 92%

“…These findings were consistent with the role of SQLE in regulating BC progression and inhibition of differentiation ( 15 ). cDNA microarrays reported that SQLE was differentially expressed in BC and that SQLE expression was increased dramatically in cancer tissues compared with in normal and cancer-adjacent normal tissues ( 18 , 19 ). In the present study, SQLE expression was directly compared in sets of matched normal breast, BC and nodal metastatic tissues using RNA-Seq and RT-qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…SQLE overexpression was more prevalent in high-grade, HER2 + and hormone receptor-negative invasive BC, and was an independently significant unfavorable prognostic biomarker in BC ( 26 ). Yu et al ( 18 ) evaluated gene expression profiles from early-onset BC tissues (age of patients, <40 years) and their adjacent normal tissues to explore the genes and prognostic factors associated with BC, revealing that SQLE expression was upregulated in BC and that high SQLE expression was associated with a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, SQLE is involved in the process by which normal mammary fibroblasts induce a reversion of the malignant phenotype in primary BC ( 16 ). SQLE overexpression is more prevalent in groups with an unfavorable prognosis of stage I/II estrogen receptor-positive (ER + ) BC ( 17 ), early-onset BC ( 18 ) and African-American patients with luminal A BC ( 19 ). Increased SQLE expression in patients with ER + BC has been associated with poor response to endocrine therapy ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

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Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer

et al. 2021

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Differentially expressed genes (DEGs) have been previously identified using massive parallel RNA sequencing in matched normal, breast cancer (BC) and nodal metastatic tissues. Squalene epoxidase (SQLE), one of these DEGs, is a key enzyme in cholesterol synthesis. The aim of the present study was to investigate the potential involvement of SQLE in the tumorigenic process of BC and to determine its association with the clinical outcome of BC. SQLE mRNA expression was measured using reverse transcription-quantitative PCR in 10 pairs of ductal carcinoma in situ (DCIS) and BC tissues and their adjacent normal tissues. Immunohistochemical staining of SQLE on tissue microarray was performed in 26 normal breast, 79 DCIS and 198 BC samples. The role of SQLE as a prognostic biomarker in patients with BC has been verified using BreastMark. SQLE mRNA expression was significantly increased in DCIS and BC tissues compared with that in their adjacent normal tissues. High SQLE expression was detected in 0, 48.1 and 40.4% of normal breast, DCIS and BC tissues, respectively. SQLE expression in DCIS and BC tissues was significantly higher than that in normal breast tissues. High SQLE expression was observed in DCIS with higher nuclear grade, comedo-type necrosis and HER2 positivity. High SQLE expression in BC was associated with larger tumor size, nodal metastases, higher stage, HER2 subtype and distant metastatic relapse. High SQLE expression was associated with poor disease-free and overall survival, and independently predicted poor disease-free survival in patients with BC. Following BreastMark analysis, high SQLE mRNA expression in BC was significantly associated with a poor prognosis in the ‘all’, lymph node negative, lymph node positive, luminal A subtype and luminal B subtype groups. Therefore, SQLE expression may be upregulated during the tumorigenic process of BC, and high SQLE expression may be a useful biomarker for predicting a poor prognosis in patients with BC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer

et al. 2021

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“…Furthermore, studies have identi ed numerous candidate biomarkers associated with the prognosis and metastasis of breast cancer [15,16]. Simultaneously, several studies have demonstrated that some microRNAs (miRNAs) and transcription factors (TFs) play critical regulatory roles in BRCA [17][18][19][20]. While many BRCA-related differentially expressed genes, microRNAs, and TFs have been studied in recent years, the detailed pathogenesis of BRCA remains unclear due to limited understanding of mRNA-miRNA-TF relationships in this oncogenic context.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Identification of Prognostic Factors Associated with Breast Cancer

Wei

Shi-peng

et al. 2020

Preprint

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Background: Breast cancer (BRCA) remains one of the most common forms of cancer and is the most prominent driver of cancer-related death among women. The mechanistic basis for BRCA, however, remains incompletely understood. In particular, the relationships between driver mutations and signaling pathways in BRCA are poorly characterized, making it difficult to identify reliable clinical biomarkers that can be employed in diagnostic, therapeutic, or prognostic contexts.Methods: First, we downloaded publically available BRCA datasets (GSE45827, GSE42568, and GSE61304) from the Gene Expression Omnibus (GEO) database. We then compared gene expression profiles between tumor and control tissues in these datasets using Venn diagrams and the GEO2R analytical tool. We further explore the functional relevance of BRCA-associated differentially expressed genes (DEGs) via functional and pathway enrichment analyses using the DAVID tool, and we then constructed a protein-protein interaction network incorporating DEGs of interest using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Modules within this PPI network were then identified using Cytoscape, leading to the identification of key candidate genes. The prognostic relevance of these candidate genes was then established through Kaplan-Meier survival analyses and further Gene Expression Profiling Interactive Analysis (GEPIA) validation. Then, key gene-target miRNA regulatory network and transcription factor-key gene regulatory relationships were established using the online miRWalk2.0, TargetScan7.2, miRDB and TRRUST tools. Moreover, four representative key molecules (AURKA, RRM2, BIRC5, and E2F1) were optionally chosen for verification by using quantitative real-time polymerase chain reaction (RT-PCR) and western blot.Results: We identified 85 BRCA-related DEGs across these three datasets. The 31 upregulated DEGs were found to be enriched for pathways and functions including mitotic nuclear division, cell division, G2/M transition of mitotic cell cycle, collagen catabolic process, endodermal cell differentiation, oocyte meiosis, ECM-receptor interactions, and p53 signaling pathway. The 54 downregulated DEGs were, in contrast, enriched in pathways and functions such as lipid metabolic processes, lipid transport, regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ions, positive regulation of cell proliferation, positive regulation of cell-matrix adhesion, tyrosine metabolism, cytochrome P450 drug metabolism, protein digestion and absorption, and PPAR signaling. We were further able to select 16 upregulated candidate genes of interest from our PPI network, and in subsequent Kaplan-Meier analyses we were able to determine that elevated expression of 14 of these genes was associated with a poorer BRCA patient prognosis. We then employed GEPIA to validate these 14 gene candidates, confirming them to all be expressed at elevated levels in BRCA relative to normal tissue controls. In addition, a regulatory network consisting of 9 genes, 10 miRNAs and 3 TFs was constructed, enabling the identification of potential biomarkers of BRCA, including AURKA, RRM2, BIRC5, and E2F1. RT-PCR results suggested that significantly elevated AURKA, RRM2 and BIRC5 mRNAs expressed in the breast cancer cells than in the normal cells. Western blot results shown that E2F1 protein was highly expressed in breast cancer cells compared to normal cells. In conclusion, these candidate molecules may offer insight regarding the underlying pathogenesis of BRCA and highlight a number of potential therapeutic avenues for the treatment of breast cancer patients.

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A comprehensive genome-based analysis identifies the anti-cancerous role of the anoikis-related gene ADH1A in modulating the pathogenesis of breast cancer

Chen,

Guo,

Chai

et al. 2024

Mol Genet Genomics

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Screening of Prognostic Factors in Early-Onset Breast Cancer

Cited by 13 publications

References 29 publications

Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer

Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer

Bioinformatics Identification of Prognostic Factors Associated with Breast Cancer

A comprehensive genome-based analysis identifies the anti-cancerous role of the anoikis-related gene ADH1A in modulating the pathogenesis of breast cancer

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