scholarly journals Model-Based Integration Analysis Revealed Presence of Novel Prognostic miRNA Targets and Important Cancer Driver Genes in Triple-Negative Breast Cancers

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 632
Author(s):  
Masood Zaka ◽  
Chris W. Sutton ◽  
Yonghong Peng ◽  
Savas Konur
Keyword(s):  
Breast Cancer ◽  
Potential Role ◽  
Triple Negative ◽  
Expression Profiles ◽  
Driver Genes ◽  
Cancer Driver ◽  
Model Based ◽  
Oncogenic Pathways ◽  
Cancer Driver Genes

Background: miRNAs (microRNAs) play a key role in triple-negative breast cancer (TNBC) progression, and its heterogeneity at the expression, pathological and clinical levels. Stratification of breast cancer subtypes on the basis of genomics and transcriptomics profiling, along with the known biomarkers’ receptor status, has revealed the existence of subgroups known to have diverse clinical outcomes. Recently, several studies have analysed expression profiles of matched mRNA and miRNA to investigate the underlying heterogeneity of TNBC and the potential role of miRNA as a biomarker within cancers. However, the miRNA-mRNA regulatory network within TNBC has yet to be understood. Results and Findings: We performed model-based integrated analysis of miRNA and mRNA expression profiles on breast cancer, primarily focusing on triple-negative, to identify subtype-specific signatures involved in oncogenic pathways and their potential role in patient survival outcome. Using univariate and multivariate Cox analysis, we identified 25 unique miRNAs associated with the prognosis of overall survival (OS) and distant metastases-free survival (DMFS) with “risky” and “protective” outcomes. The association of these prognostic miRNAs with subtype-specific mRNA genes was established to investigate their potential regulatory role in the canonical pathways using anti-correlation analysis. The analysis showed that miRNAs contribute to the positive regulation of known breast cancer driver genes as well as the activation of respective oncogenic pathway during disease formation. Further analysis on the “risk associated” miRNAs group revealed significant regulation of critical pathways such as cell growth, voltage-gated ion channel function, ion transport and cell-to-cell signalling. Conclusion: The study findings provide new insights into the potential role of miRNAs in TNBC disease progression through the activation of key oncogenic pathways. The results showed previously unreported subtype-specific prognostic miRNAs associated with clinical outcome that may be used for further clinical evaluation.

Cancer driver genes in luminal and triple negative breast cancer from young women.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13527-e13527
Author(s):  
Simone Maistro ◽  
Ana Carolina Ribeiro Chaves De Gouvea ◽  
Gláucia Fernanda de Lima Pereira ◽  
Maria Lucia Hirata Katayama ◽  
Lívia Munhoz Rodrigues ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Young Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Driver Genes ◽  
Cancer Driver ◽  
Cancer Driver Genes

scholarly journals The potential role of cofilin-1 in promoting triple negative breast cancer (TNBC) metastasis via the extracellular vesicles (EVs)

2022 ◽  
Vol 15 (1) ◽  
pp. 101247
Author(s):  
Jane Howard ◽  
Chia Yin Goh ◽  
Karolina Weiner Gorzel ◽  
Michaela Higgins ◽  
Amanda McCann
Keyword(s):  
Breast Cancer ◽  
Extracellular Vesicles ◽  
Triple Negative Breast Cancer ◽  
Potential Role ◽  
Triple Negative

Abstract P3-05-03: Identification of epigenetically silenced breast cancer driver genes

2019 ◽  
Author(s):  
S Panjarian ◽  
J Madzo ◽  
C Slater ◽  
J Jelinek ◽  
X Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Driver Genes ◽  
Cancer Driver ◽  
Cancer Driver Genes

scholarly journals Model-based analysis of positive selection significantly expands the list of cancer driver genes, including RNA methyltransferases

2018 ◽  
Author(s):  
Siming Zhao ◽  
Jun Liu ◽  
Pranav Nanga ◽  
Yuwen Liu ◽  
A. Ercument Cicek ◽  
...  
Keyword(s):  
Positive Selection ◽  
Cancer Biology ◽  
Spatial Clustering ◽  
Strong Support ◽  
Driver Gene ◽  
Driver Genes ◽  
Cancer Driver ◽  
Model Based ◽  
Cancer Driver Genes ◽  
Model Based Analysis

AbstractIdentifying driver genes is a central problem in cancer biology, and many methods have been developed to identify driver genes from somatic mutation data. However, existing methods either lack explicit statistical models, or rely on very simple models that do not capture complex features in somatic mutations of driver genes. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a more comprehensive model-based approach to driver gene identification. This new method explicitly models, at the single-base level, the effects of positive selection in cancer driver genes as well as highly heterogeneous background mutational process. Its selection model captures elevated mutation rates in functionally important sites using multiple external annotations, as well as spatial clustering of mutations. Its background mutation model accounts for both known covariates and unexplained local variation. Simulations under realistic evolutionary models demonstrate that driverMAPS greatly improves the power of driver gene detection over state-of-the-art approaches. Applying driverMAPS to TCGA data across 20 tumor types identified 159 new potential driver genes. Cross-referencing this list with data from external sources strongly supports these findings. The novel genes include the mRNA methytransferases METTL3-METTL14, and we experimentally validated METTL3 as a potential tumor suppressor gene in bladder cancer. Our results thus provide strong support to the emerging hypothesis that mRNA modification is an important biological process underlying tumorigenesis.

CircPLK1 sponges miR-296-5p to facilitate triple-negative breast cancer progression

Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1163-1176 ◽  
Author(s):  
Yanan Kong ◽  
Lu Yang ◽  
Weidong Wei ◽  
Ning Lyu ◽  
Yutian Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Proliferation And Metastasis ◽  
Underlying Mechanisms

Aim: To investigate the role of circRNAs in triple-negative breast cancer (TNBC) and the underlying mechanisms. Materials & methods: We performed circRNA microarrays to explore the expression profiles of TNBC cell lines. Experiments in vitro and in vivo were conducted to explore the effects of circPLK1 on tumor proliferation and metastasis as well as the interaction between circPLK1, miR-296-5p and PLK1 in TNBC. Results & conclusion: CircPLK1 was significantly upregulated in TNBC and associated with poor survivals. CircPLK1 knockdown inhibited cell growth and invasion in vitro as well as tumor occurrence and metastasis in vivo. CircPLK1-miR-296-5p- PLK1 axis regulates tumor progression by ceRNA mechanism in TNBC, indicating that circPLK1 may serve as a prognostic factor and novel therapeutic target for TNBC.

scholarly journals Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Luis Zapata ◽  
Hana Susak ◽  
Oliver Drechsel ◽  
Marc R. Friedländer ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Positive Selection ◽  
Driver Genes ◽  
Cancer Driver ◽  
Cancer Driver Genes ◽  
Chromatin Modifiers

scholarly journals Comprehensive analysis of the cancer driver genes in breast cancer demonstrates their roles in cancer prognosis and tumor microenvironment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiao-wei Du ◽  
Gao Li ◽  
Juan Liu ◽  
Chun-yan Zhang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Risk Group ◽  
Cancer Prognosis ◽  
Driver Gene ◽  
Driver Genes ◽  
Cancer Driver ◽  
Cancer Driver Gene ◽  
Cancer Driver Genes ◽  
Patient Prognosis

Abstract Background Breast cancer is the most common malignancy in women. Cancer driver gene-mediated alterations in the tumor microenvironment are critical factors affecting the biological behavior of breast cancer. The purpose of this study was to identify the expression characteristics and prognostic value of cancer driver genes in breast cancer. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets are used as the training and test sets. Classified according to cancer and paracancerous tissues, we identified differentially expressed cancer driver genes. We further screened prognosis-associated genes, and candidate genes were submitted for the construction of a risk signature. Functional enrichment analysis and transcriptional regulatory networks were performed to search for possible mechanisms by which cancer driver genes affect breast cancer prognosis. Results We identified more than 200 differentially expressed driver genes and 27 prognosis-related genes. High-risk group patients had a lower survival rate compared to the low-risk group (P<0.05), and risk signature showed high specificity and sensitivity in predicting the patient prognosis (AUC 0.790). Multivariate regression analysis suggested that risk scores can independently predict patient prognosis. Further, we found differences in PD-1 expression, immune score, and stromal score among different risk groups. Conclusion Our study confirms the critical prognosis role of cancer driver genes in breast cancer. The cancer driver gene risk signature may provide a novel biomarker for clinical treatment strategy and survival prediction of breast cancer.

Functional annotation of cancer driver genes in breast cancer patient-derived xenografts to identify a novel target for PARP inhibitors.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23192-e23192 ◽  
Author(s):  
Xiaosong Zhang ◽  
Meng Li ◽  
Olga Momcilovic ◽  
Andrew Beardsley ◽  
Roman Camarda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Functional Annotation ◽  
Parp Inhibitors ◽  
Driver Genes ◽  
Cancer Driver ◽  
Cancer Driver Genes ◽  
Novel Target

scholarly journals Knockdown of PC4 Increases Chemosensitivity of Oxaliplatin in Triple Negative Breast Cancer by Supressing mTOR Pathway

2020 ◽  
Author(s):  
Qing Wang ◽  
Le Ma ◽  
Long Chen ◽  
Hongdan Chen ◽  
Min Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Potential Role ◽  
Triple Negative ◽  
Mtor Pathway ◽  
Promising Therapeutic Target ◽  
Response To Chemotherapy

Abstract Background: The response to chemotherapy is an important factor in the prognosis of patients with triple negative breast cancer (TNBC). Human positive coactivator 4 (PC4) is a multifunctional nuclear protein, that is highly expressed in various tumors including breast cancer and shows a potential role in cancer development and progression. However, the role of PC4 in chemotherapeutic responses of TNBC remains unclear. Our work aim to identify the role of PC4 in the response to oxaliplatin (Oxa) of TNBC patients.Results: We found that PC4 is significantly upregulated in TNBC cells compared with non-TNBC cells, implying its potential role in TNBC. Then, in vivo and in vitro studies revealed that knockdown of PC4 increased chemosensitivity of Oxa in TNBC by supressing mTOR pathway.Conclusions: Our findings demonstrated the signatures of PC4 in the chemotherapeutic response of TNBC, and indicated that PC4 might be a promising therapeutic target for TNBC.

scholarly journals Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Shuai Wu ◽  
Rui Su ◽  
Hongyan Jia
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Triple Negative Breast Cancer ◽  
Potential Role ◽  
Triple Negative ◽  
Targeting Therapy ◽  
A Cell

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Currently, targeting therapy makes great advances for the treatment of TNBC, whereas more effective therapeutic targets are urgently needed. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is known as a cell cycle regulator. CCNB2 is synthesized at G1 phase in cancer cells and downregulated at anaphase. The defects of CCNB2 led to the abnormal cell cycle and tumorigenesis. Though there are wide effects of CCNB2 on multiple types of tumors, the potential role of CCNB2 in TNBC progression is still unclear. Herein, we found that CCNB2 was highly expressed in human TNBC tissues and correlated with the prognosis and clinical pathological features including tumor size ( p = 0.022 ∗ ) and pTNM stage ( p = 0.021 ∗ ) of patients with TNBC. CCNB2 could promote the proliferation of TNBC cells in vitro and in mice. Our findings therefore confirmed the involvement of CCNB2 in TNBC progression and provided the evidence that CCNB2 could serve as a promising molecular target of TNBC.

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