RRM1, TUBB3, TOP2A, CYP19A1, CYP2D6: Difference between mRNA and protein expression in predicting prognosis of breast cancer patients

Xu, Yingchun; Zhang, Fengchun; Li, Junjian; Dai, Jing; Liu, Qiang; Tang, Lei; Ma, Yue; Xu, Qi; Lin, Xiaolin; Fan, Hongbin; Wang, Hongxia

doi:10.3892/or.2015.4183

Cited by 21 publications

(18 citation statements)

References 35 publications

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“…TUBB3 is mainly expressed in the nucleus, and immunohistochemistry showing brown granules indicates positive expression (18). Research has confirmed the correlation between TUBB3 expression and the chemosensitivity of taxanes, and TUBB3 has been confirmed as a prognostic predictor of various solid tumors such as breast, ovarian, prostate and lung cancer (6). In the present study, the DFS and OS of human breast cancer patients with TUBB3-or TOP2A-positive tumors were lower than the DFS and OR of the patients with TUBB3-or TOP2A-negative tumors.…”

Section: Discussionsupporting

confidence: 74%

“…tissues is also related to the sensitivity of chemotherapeutic agents (6). Research has shown that TUBB3 expression is closely related to drug resistance of taxanes.…”

Section: Suppression Of Pten/akt Signaling Decreases the Expression Omentioning

confidence: 99%

“…In recent years, researchers have given more attention to the relationship between molecular markers and chemotherapeutic drug resistance, and have achieved some results (6). Platinum agents are a group structurally similar to bifunctional alkylating agents, which forms a complex with bases on nucleophilic groups by covalent bonding, resulting in DNA replication and transcription by structural changes and disorders, thereby inhibiting cell division (7).…”

Section: Introductionmentioning

confidence: 99%

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Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways

et al. 2017

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The aim of the present study was to evaluate the effects of PTEN/AKT signaling on TUBB3 and TOP2A expression and on the subsequent cell growth of human breast cancer MCF-7 cells. We found that the disease-free survival (DFS) and overall survival (OS) of breast cancer patients with TUBB3‑positive tumors were lower than these rates in the patients with TUBB3-negative tumors. Meanwhile, DFS and OS of breast cancer patients with TOP2A-positive tumors were also lower than these rates in patients with TOP2A-negative tumors. Suppression of PTEN reduced the protein expression of TUBB3 and TOP2A in MCF-7 cells. Suppression of PTEN also reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells. Moreover, an increase in ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells following suppression of PTEN. Suppression of phosphorylation-AKT (p-AKT) reduced the protein expression of TUBB3 and TOP2A in the MCF-7 cells. Suppression of p-AKT also reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells. Then, ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells following suppression of p-AKT. These results suggest that PTEN/AKT signaling affects the expression of TUBB3 and TOP2A reducing cell growth and inducing apoptosis of human breast cancer MCF-7 cells through ATP and caspase-3 signaling pathways. TUBB3 and TOP2A may be promising prognostic markers for the efficacy of adjuvant cisplatin-based chemotherapy.

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Section: Discussionsupporting

confidence: 74%

“…tissues is also related to the sensitivity of chemotherapeutic agents (6). Research has shown that TUBB3 expression is closely related to drug resistance of taxanes.…”

Section: Suppression Of Pten/akt Signaling Decreases the Expression Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways

et al. 2017

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“…Study had demonstrated that TOP2A identified and provided epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer [26] . Moreover, we could find the prognostic value of TOP2A in nasopharyngeal carcinoma and breast cancer [27] , [28] . Ubiquitin-conjugating enzyme E2 C ( UBE2C ), a member of the E2 ubiquitin-conjugating enzyme family, was required for the destruction of mitotic cyclins and for cell cycle progression and may be involved in cancer progression.…”

Section: Discussionmentioning

confidence: 96%

Co-expression network analysis identified six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma (ccRCC)

et al. 2017

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Human clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney tumors. We constructed a weighted gene co-expression network to identify gene modules associated with clinical features of ccRCC (n = 97). Six hub genes (CCNB2, CDC20, CEP55, KIF20A, TOP2A and UBE2C) were identified in both co-expression and protein-protein interaction (PPI) networks, which were highly correlated with pathologic stage. The significance of expression of the hub genes in ccRCC was ranked top 4 among all cancers and correlated with poor prognosis. Functional analysis revealed that the hub genes were significantly enriched in cell cycle regulation and cell division. Gene set enrichment analysis suggested that the samples with highly expressed hub gene were correlated with cell cycle and p53 signaling pathway. Taken together, six hub genes were identified to be associated with progression and prognosis of ccRCC, and they might lead to poor prognosis by regulating p53 signaling pathway.

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“…DNA topoisomerase 2-alpha (TOP2A) gene encodes a protein that controls and alters topologic states of DNA during the process of transcription. TOP2A is a signi cant prognostic factor in predicting the breast cancer patients' OS, and low expression of TOP2A has been associated with a better clinical outcome [49]. In addition TOP2A ampli cation or deletion is also known to enhance responsiveness to anthracycline-containing chemotherapy regimens relative to non-anthracycline regimens [50].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of FN1, Activation of Maturation Promoting Factor and Associated Signaling Pathway Facilitates Epithelial-Mesenchymal Transition, Inhibits Apoptosis and Elevates Proliferation Rate of Breast Cancer Cells: In Silico Analysis of Microarray Datasets

Hameed

Ejaz

2020

Preprint

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Background: Knowing that the molecular mechanisms underlying breast cancer (BC) are not yet fully understood it was considered worth to launch investigation for the detection of key molecular pathways and associated genes and proteins. Methods: In total two microarray based datasets (GSE10810 and GSE29431), consisting of 89 breast cancer samples and 31 controls, were retrieved from the Gene Expression Omnibus (GEO) database and processed to identify the differentially expressed genes (DEGs). The pathway and functional enrichment analyses of DEGs were performed using DAVID online tool. Protein-Protein interaction (PPI) network was constructed using an online tool STRING and visualized through Cytoscape software to identify the significant module and hub genes via MCODE and Cytohubba applications. The identified hub genes were then further analyzed to document their response in Kaplan-Meier (KM) survival curve analysis, investigate differential expression profile and its correlation with promoter’s methylation status, and finally for the construction of the gene-drug interaction network. Results: In total 449 DEGs were detected including 151 up-regulated and 298 down-regulated genes. The identified DEGs were enriched in various cancer related biological functions and pathways. Based on PPI network analysis of the DEGs, six hub genes, CDK1, FN1, AURKA, CCNB2, BIRC5, and TOP2A, were correlated with worse overall survival (OS) of the breast cancer patients. Conclusion: The extensive in silico analysis has been helpful to evaluate evidence highlighting the prominent role played by the identified hub genes in stimulating breast tumor growth through the activation of Maturation Promoting Factor (MPF), PI3K/AKT signaling, and associated pathways that could be targeted for devising effective treatment strategies.

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RRM1, TUBB3, TOP2A, CYP19A1, CYP2D6: Difference between mRNA and protein expression in predicting prognosis of breast cancer patients

Abstract: Abstract. The study investigated the clinical significance of RRM1 (ribonucleoside reductase subunit M1), TUBB3

Cited by 21 publications

References 35 publications

Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways

Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways

Co-expression network analysis identified six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma (ccRCC)

Up-regulation of FN1, Activation of Maturation Promoting Factor and Associated Signaling Pathway Facilitates Epithelial-Mesenchymal Transition, Inhibits Apoptosis and Elevates Proliferation Rate of Breast Cancer Cells: In Silico Analysis of Microarray Datasets

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