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ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics.

ABSTRACT: Background:Recently, long non-coding RNAs (lncRNAs) are important populations of non-coding RNAs with defined key roles in normal breast development as well as breast tumorigenesis. Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis because of highly invasive and no specific drug treatment yet. Breast cancer stems cells (BCSCs) cause a high risk of invasion, metastasis and drug resistance for breast cancer patients. Methods:Two microarrays of BCSCs and no-BCSCs were isolated from mammosphere-3D-cultured MCF-7 cells, differentially expressed lncRNAs (DELs) were screened out by Gene Expression Omnibus (GEO). Gene ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to analyze DELs features. Using the STRING database to analyze DELs interaction network module to further screen the hub lncRNAs related to tumor stemness and make functional annotations. The expressions of hub DELs were validated using data from The Cancer Genome Atlas database. In addition, the expression analysis and survival analysis were conducted using GEO was utilized to analyze DELs in TNBC using GEPIA database. Results:A total of 143 aberrantly expressed lncRNAs in BCSCs were identified, and 25 lncRNAs were downregulated and 118 lncRNAs were upregulated compared to non-BCSCs. Up- and downregulated top 3 lncRNAs were selected and verified by RT-PCR. Notably, GO enrichment analysis and KEGG pathway analysis indicated that RNA transport, spliceosome, oxidative phosphorylation, NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways may serve important roles in BCSCs. Additionally, the function loss assay indicated that ZGRF1 positively upregulated phenotype and biological functions of BCSCs in vitro. Collectively, our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer. Conclusion:Our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer. ZGRF1 expression is upregulated in TNBC patients and has a poor prognosis, which can be promising biomarkers.

SUBMITTER: Ge W

PROVIDER: S-EPMC7138618 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics.

Ge Weiyu W Jiang Mengyi M Zhang Fengchun F Ma Yue Y Wang Hongxia H Xu Yingchun Y

OncoTargets and therapy 20200403

<h4>Background</h4>Recently, long non-coding RNAs (lncRNAs) are important populations of non-coding RNAs with defined key roles in normal breast development as well as breast tumorigenesis. Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis because of highly invasive and no specific drug treatment yet. Breast cancer stems cells (BCSCs) cause a high risk of invasion, metastasis and drug resistance for breast cancer patients.<h4>Methods</h4>Two microarra ...[more]

PMID: 32308418

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Project description:IntroductionTriple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs.Materials and methodsThe surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed.ResultsPositive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P?=?0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P?=?0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both P<0.001). Similarly it was also associated with shorter overall survival (OS)(P?=?0.003 in LN+ cases; P?=?0.018 in LN- cases). In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P?=?0.008). Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P?=?0.002). However, neither CLDN4 nor CLDN7 expression was associated with survival.ConclusionIn TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

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ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics.

Publications

ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics.

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