Abstract
CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network. Following up on our previous observation that CDK8, CDK19 and CCNC RNA expression is associated with shorter relapse-free survival (RFS) in breast cancer, we now found by immunohistochemical analysis that CDK8/19 protein is overexpressed in invasive ductal carcinomas relative to non-malignant mammary tissues. Meta-analysis of transcriptomic data revealed that higher CDK8 expression is associated with shorter RFS in all molecular subtypes of breast cancer. These correlations were much stronger in patients who underwent systemic adjuvant therapy, suggesting that CDK8 impacts the failure of systemic therapy. The same associations were found for CDK19, CCNC and MED13. In contrast, MED12 showed the opposite association with a longer RFS. The expression levels of CDK8 in breast cancer samples were directly correlated with the expression of MYC, as well as CDK19, CCNC and MED13 but inversely correlated with MED12. CDK8, CDK19 and CCNC expression was strongly increased and MED12 expression was decreased in tumors with mutant p53. Gene amplification is the most frequent type of genetic alterations of CDK8, CDK19, CCNC and MED13 in breast cancers (9.7% of which have amplified MED13), whereas point mutations are more common in MED12. These results suggest that the expression of CDK8 and its interactive genes has a profound impact on the response to adjuvant therapy in breast cancer in accordance with the role of CDK8 in chemotherapy-induced tumor-supporting paracrine activities.
Keywords: Breast cancer, CDK8, CDK19, Cyclin C, MED12, MED13, microarray data mining, tissue microarrays.
Current Cancer Drug Targets
Title:Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer
Volume: 15 Issue: 8
Author(s): Eugenia V. Broude, Balázs Gyorffy, Alexander A. Chumanevich, Mengqian Chen, Martina S. J. McDermott, Michael Shtutman, James F. Catroppo and Igor B. Roninson
Affiliation:
Keywords: Breast cancer, CDK8, CDK19, Cyclin C, MED12, MED13, microarray data mining, tissue microarrays.
Abstract: CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network. Following up on our previous observation that CDK8, CDK19 and CCNC RNA expression is associated with shorter relapse-free survival (RFS) in breast cancer, we now found by immunohistochemical analysis that CDK8/19 protein is overexpressed in invasive ductal carcinomas relative to non-malignant mammary tissues. Meta-analysis of transcriptomic data revealed that higher CDK8 expression is associated with shorter RFS in all molecular subtypes of breast cancer. These correlations were much stronger in patients who underwent systemic adjuvant therapy, suggesting that CDK8 impacts the failure of systemic therapy. The same associations were found for CDK19, CCNC and MED13. In contrast, MED12 showed the opposite association with a longer RFS. The expression levels of CDK8 in breast cancer samples were directly correlated with the expression of MYC, as well as CDK19, CCNC and MED13 but inversely correlated with MED12. CDK8, CDK19 and CCNC expression was strongly increased and MED12 expression was decreased in tumors with mutant p53. Gene amplification is the most frequent type of genetic alterations of CDK8, CDK19, CCNC and MED13 in breast cancers (9.7% of which have amplified MED13), whereas point mutations are more common in MED12. These results suggest that the expression of CDK8 and its interactive genes has a profound impact on the response to adjuvant therapy in breast cancer in accordance with the role of CDK8 in chemotherapy-induced tumor-supporting paracrine activities.
Export Options
About this article
Cite this article as:
V. Broude Eugenia, Gyorffy Balázs, A. Chumanevich Alexander, Chen Mengqian, S. J. McDermott Martina, Shtutman Michael, F. Catroppo James and B. Roninson Igor, Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer, Current Cancer Drug Targets 2015; 15 (8) . https://dx.doi.org/10.2174/156800961508151001105814
DOI https://dx.doi.org/10.2174/156800961508151001105814 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Gallium-68 in Medical Imaging
Current Radiopharmaceuticals Recent Developments in Receptor-Selective Retinoids
Current Pharmaceutical Design Anti-Cancer/Anti-Tumor
Current Bioactive Compounds Perioperative Safety of Warfarin Therapy and Reversal
Current Drug Safety Benzo[d]imidazol-5-yl)-5-(substituted)-1,3,4-Oxadiazoles: Synthesis, Anticancer, Antimicrobial and In Silico Studies
Letters in Drug Design & Discovery Effect of Intestinal Flora Clearance on Liver Proteomics in Mice
Current Proteomics Biologics: An Update and Challenge of Their Pharmacokinetics
Current Drug Metabolism Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Assessment of Response to Treatment and Follow-Up in Gastroenteropancreatic Neuroendocrine Neoplasms
Endocrine, Metabolic & Immune Disorders - Drug Targets Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance
Anti-Cancer Agents in Medicinal Chemistry Microdosing, Imaging Biomarkers and SPECT: A Multi-Sided Tripod to Accelerate Drug Development
Current Pharmaceutical Design Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry Low Molecular Weight and Oligomeric Chitosans and Their Bioactivities
Current Topics in Medicinal Chemistry Cellular Energetical Actions of “Chemical” and “Surgical” Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function
Current Neuropharmacology New Cell Therapy Using Bone Marrow-Derived Stem Cells/Endothelial Progenitor Cells to Accelerate Neovascularization in Healing of Experimental Ulcerative Colitis
Current Pharmaceutical Design Angiogenesis Inhibition: State of the Art, Forgotten Strategies and New Perspectives in Cancer Therapy
Current Cancer Therapy Reviews Structural Comparison of Gene Relevance Networks for Breast Cancer Tissues in Different Grades
Combinatorial Chemistry & High Throughput Screening Heat Shock Protein 90 Inhibitors as Therapeutic Agents
Recent Patents on Anti-Cancer Drug Discovery Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties
Current Pharmaceutical Biotechnology Serum Amyloid A and Its Potential Physiological / Pathological Functions - an Overview of Patents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery