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1
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Halim A, Kim B, Kenyon E, Moore A. miR-10b as a Clinical Marker and a Therapeutic Target for Metastatic Breast Cancer. Technol Cancer Res Treat 2025; 24:15330338251339256. [PMID: 40397123 PMCID: PMC12099151 DOI: 10.1177/15330338251339256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/25/2025] [Accepted: 04/14/2025] [Indexed: 05/22/2025] Open
Abstract
Despite advances in cancer detection and treatment, metastatic breast cancer continues to carry a poor prognosis due to the lack of diagnostic and therapeutic resources that are specific to the metastatic process. MicroRNA-10b (miR-10b) is a small, noncoding RNA that is the focus of many studies due to its unique role as a driver of metastasis. The pathways it is involved in and the properties it confers have been reviewed previously and, collectively, are suggestive of the potential of miR-10b as a clinical marker and as a therapeutic target specific to metastatic disease. With the goal of application of our understanding of miR-10b to the clinic, in this mini-review, we highlight the studies that support the utility of miR-10b for these translational purposes.
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Affiliation(s)
- Alan Halim
- Precision Health Program, Michigan State University, East Lansing, MI, USA
| | - Bryan Kim
- Precision Health Program, Michigan State University, East Lansing, MI, USA
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Elizabeth Kenyon
- Precision Health Program, Michigan State University, East Lansing, MI, USA
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Anna Moore
- Precision Health Program, Michigan State University, East Lansing, MI, USA
- Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
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2
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Khalifa A, Guijarro A, Nencioni A. Advances in Diet and Physical Activity in Breast Cancer Prevention and Treatment. Nutrients 2024; 16:2262. [PMID: 39064705 PMCID: PMC11279876 DOI: 10.3390/nu16142262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 07/07/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
There is currently a growing interest in diets and physical activity patterns that may be beneficial in preventing and treating breast cancer (BC). Mounting evidence indicates that indeed, the so-called Mediterranean diet (MedDiet) and regular physical activity likely both help reduce the risk of developing BC. For those who have already received a BC diagnosis, these interventions may decrease the risk of tumor recurrence after treatment and improve quality of life. Studies also show the potential of other dietary interventions, including fasting or modified fasting, calorie restriction, ketogenic diets, and vegan or plant-based diets, to enhance the efficacy of BC therapies. In this review article, we discuss the biological rationale for utilizing these dietary interventions and physical activity in BC prevention and treatment. We highlight published and ongoing clinical studies that have applied these lifestyle interventions to BC patients. This review offers valuable insights into the potential application of these dietary interventions and physical activity as complimentary therapies in BC management.
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Affiliation(s)
- Amr Khalifa
- Department of Internal Medicine and Medical Specialties, University of Genoa, Viale Benedetto XV 6, 16132 Genoa, Italy;
| | - Ana Guijarro
- Department of Internal Medicine and Medical Specialties, University of Genoa, Viale Benedetto XV 6, 16132 Genoa, Italy;
| | - Alessio Nencioni
- Department of Internal Medicine and Medical Specialties, University of Genoa, Viale Benedetto XV 6, 16132 Genoa, Italy;
- IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
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3
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González-Martínez C, Garrido-Navas C, Alcaide-Lucena M, Hidalgo JL, Ortega FG, Serrano MJ. microRNAs signature in relapse metastasis and de novo metastasis of breast cancer. A systematic review. Crit Rev Oncol Hematol 2023:104060. [PMID: 37353177 DOI: 10.1016/j.critrevonc.2023.104060] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/12/2023] [Accepted: 06/19/2023] [Indexed: 06/25/2023] Open
Abstract
miRNAs have been widely identified as important players in cancer development and progression. Metastasis in breast cancer can occur as relapse of a treated primary tumour or at the time of diagnosis of the tumour. The aim of this review is to show if both metastasis are different molecular entities characterised by different miRNA signatures that could be studied as specific biomarkers for each entity. For this, we systematically searched the PubMed, Scopus and Web of Science databases. After searching and reviewing the literature, a total of 30 records were included in this review. Results showed a genetic signature including a total of 5 upregulated miRNAs in metastasis compared with early stages. Of them, miR-23b and miR-200c were exclusively present in relapse metastasis. Finally, we proposed a molecular signature for future studies that can be used as a complementary tool at clinical trials for the diagnosis and characterization of metastasis.
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Affiliation(s)
- Coral González-Martínez
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; IBS Granada, Institute of Biomedical Research. Avenida de Madrid 15, 18012 Granada, Spain; Department of Legal Medicine, University of Granada, Av. de la Investigación, 11, 18071 Granada, Spain
| | - Carmen Garrido-Navas
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; IBS Granada, Institute of Biomedical Research. Avenida de Madrid 15, 18012 Granada, Spain
| | - Miriam Alcaide-Lucena
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; General Surgery and Digestive System Unit, Hospital Clínico San Cecilio, 18016 Granada, Spain
| | - J López Hidalgo
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; IBS Granada, Institute of Biomedical Research. Avenida de Madrid 15, 18012 Granada, Spain; Pathological Anatomy Unit, Hospital Clínico San Cecilio, 18016 Granada, Spain
| | - Francisco Gabriel Ortega
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; IBS Granada, Institute of Biomedical Research. Avenida de Madrid 15, 18012 Granada, Spain.
| | - María José Serrano
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. Avenida de la Ilustracion 114, 18016 Granada, Spain; IBS Granada, Institute of Biomedical Research. Avenida de Madrid 15, 18012 Granada, Spain; Integral Oncology Division, Hospital Virgen de las Nieves, 18014 Granada, Spain.
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4
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Huang Z, Zhen S, Jin L, Chen J, Han Y, Lei W, Zhang F. miRNA-1260b Promotes Breast Cancer Cell Migration and Invasion by Downregulating CCDC134. Curr Gene Ther 2023; 23:60-71. [PMID: 36056852 DOI: 10.2174/1566523222666220901112314] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/25/2022] [Accepted: 08/02/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Breast cancer (BRCA) is the most common type of cancer among women worldwide. MiR-1260b has been widely demonstrated to participate in multiple crucial biological functions of cancer tumorigenesis, but its functional effect and mechanism in human breast cancer have not been fully understood. METHODS qRT-PCR was used to detect miR-1260b expression in 29 pairs of breast cancer tissues and normal adjacent tissues. Besides, the expression level of miR-1260b in BRCA cells was also further validated by qRT-PCR. miR-1260b played its role in the prognostic process by using Kaplan-Meier curves. In addition, miR-1260b knockdown and target gene CCDC134 overexpression model was constructed in cell line MDA-MB-231. Transwell migration and invasion assay was performed to analyze the effect of miR-1260b and CCDC134 on the biological function of BRCA cells. TargetScan and miRNAWalk were used to find possible target mRNAs. The relationship between CCDC134 and immune cell surface markers was analyzed using TIMER and database and the XIANTAO platform. GSEA analysis was used to identify possible CCDC134-associated molecular mechanisms and pathways. RESULTS In the present study, miR-1260b expression was significantly upregulated in human breast cancer tissue and a panel of human breast cancer cell lines, while the secretory protein coiled-coil domain containing 134 (CCDC134) exhibited lower mRNA expression. High expression of miR-1260b was associated with poor overall survival among the patients by KM plot. Knockdown of miR-1260b significantly suppressed breast cancer cell migration and invasion and yielded the opposite result. In addition, overexpression of CCDC134 could inhibit breast cancer migration and invasion, and knockdown yielded the opposite result. There were significant positive correlations of CCDC134 with CD25 (IL2RA), CD80 and CD86. GSEA showed that miR-1260b could function through the MAPK pathway by downregulating CCDC134. CONCLUSION Collectively, these results suggested that miR-1260b might be an oncogene of breast cancer and might promote the migration and invasion of BRCA cells by down-regulating its target gene CCDC134 and activating MAPK signaling pathway as well as inhibiting immune function and causing immune escape in human breast cancer.
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Affiliation(s)
- Zhijian Huang
- Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Shijian Zhen
- Department of Pathology, The First Affiliated Hospital of Hunan Traditional Chinese Medical College (Hunan Province Directly Affiliated TCM Hospital), Zhuzhou 412000, China
| | - Liangzi Jin
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
| | - Jian Chen
- Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Yuanyuan Han
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
| | - Wen Lei
- Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Fuqing Zhang
- Department of Aenethesiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
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Sengupta P, Choudhury H, Dutta S, Jacob S, Kesharwani P, Gorain B. Current Strategies in Breast Cancer Therapy: Role of Epigenetics and Nanomedicine. PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION 2022; 39. [DOI: 10.1002/ppsc.202100276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Indexed: 01/06/2025]
Abstract
AbstractBreast cancer (BC), the most common cancer in women, is incurable due to metastatic spread to distant organs. The existence of epigenetic dysregulation has been shown to contribute to the progression and even metastasize through the transition from epithelial to mesenchymal. Behind failure strategies of conventional treatments, fruitful outcomes of epigenetic drugs have provided the hope of solid tumor management where the reversal of acquired resistance of the cancer cells is possible by epigenome regulation. Several agents have been identified to target epigenetic regulators in the cancer cells exhibiting remarkable potential against solid tumors, including BC. However, unnecessary systemic exposure, solubility issues, and unsuitability for diseased conditions using conventional delivery systems limit their use as cancer therapeutics. The progression of nanotechnology in pharmaceutical delivery has revolutionized cancer therapy, where specific, targeted and efficient delivery of epigenetic agents for alteration of cancerous conditions are ensured. In this review, a focus is made on epigenetic alteration in BC condition with the deliverable potential of the nanocarriers toward the breast tumor microenvironment for proper management. The significance of targeting and controlled release of therapeutics in the improved targeting of cancer cells is highlighted.
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Affiliation(s)
- Pallav Sengupta
- Department of Physiology Faculty of Medicine, Biosciences and Nursing MAHSA University SP2, Bandar Saujana Putra Jenjarom Selangor 42610 Malaysia
- School of Medical Sciences Bharath Institute of Higher Education and Research (BIHER) Selaiyur Chennai Tamil Nadu 600126 India
| | - Hira Choudhury
- Department of Pharmaceutical Technology School of Pharmacy International Medical University Bukit Jalil Kuala Lumpur, Federal Territory of Kuala Lumpur 57000 Malaysia
| | - Sulagna Dutta
- School of Medical Sciences Bharath Institute of Higher Education and Research (BIHER) Selaiyur Chennai Tamil Nadu 600126 India
- Department of Oral Biology and Biomedical Sciences Faculty of Dentistry MAHSA University SP2 Bandar Saujana Putra Jenjarom Selangor 42610 Malaysia
| | - Shery Jacob
- Department of Pharmaceutical Sciences College of Pharmacy Gulf Medical University Ajman 4184 United Arab Emirates
| | - Prashant Kesharwani
- Department of Pharmaceutics School of Pharmaceutical Education and Research Jamia Hamdard New Delhi 110062 India
| | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology Birla Institute of Technology Mesra Ranchi Jharkhand 835215 India
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6
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Wu S, Pan R, Lu J, Wu X, Xie J, Tang H, Li X. Development and Verification of a Prognostic Ferroptosis-Related Gene Model in Triple-Negative Breast Cancer. Front Oncol 2022; 12:896927. [PMID: 35719954 PMCID: PMC9202593 DOI: 10.3389/fonc.2022.896927] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/02/2022] [Indexed: 11/14/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is the subtype with the worst prognosis of breast cancer. Ferroptosis, a novel iron-dependent programmed cell death, has an increasingly important role in tumorigenesis and development. However, there is still a lack of research on the relationship between ferroptosis-related genes and the prognosis of TNBC. In this study, we obtained the gene expression profile of TNBC patients and matched clinical data from The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis was used to screen out ferroptosis-related genes associated with TNBC prognosis. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was employed to establish a prognostic prediction model. A 15-ferroptosis-related gene prognostic prediction model was developed, which classified patients into low-risk (LR) or high-risk (HR) groups. Kaplan-Meier analysis results showed that the prognosis of the LR group was better. The receiver operating characteristic (ROC) curve also confirmed the satisfactory predictive ability of this model. Evaluation of the immune microenvironment of TNBC patients in the HR and LR group suggested these 15 ferroptosis-related genes might affect the prognosis of TNBC by regulating the tumor microenvironment. Our prognostic model can provide a theoretical basis for accurate prognosis prediction of TNBC in clinical practice.
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Affiliation(s)
- Song Wu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ruilin Pan
- Department of Breast Surgery, The First People's Hospital of Foshan, Foshan, China
| | - Jibu Lu
- Department of Breast Surgery, The First People's Hospital of Foshan, Foshan, China
| | - Xiaoling Wu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Jingdong Xie
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hailin Tang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xing Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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7
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Pouya FD, Rasmi Y, Gazouli M, Zografos E, Nemati M. MicroRNAs as therapeutic targets in breast cancer metastasis. Drug Deliv Transl Res 2022; 12:1029-1046. [PMID: 33987801 DOI: 10.1007/s13346-021-00999-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2021] [Indexed: 12/24/2022]
Abstract
Breast cancer is a complex disease with multiple risk factors involved in its pathogenesis. Among these factors, microRNAs are considered for playing a fundamental role in the development and progression of malignant breast tumors. In recent years, various studies have demonstrated that several microRNAs exhibit increased or decreased expression in metastatic breast cancer, acting as indicators of metastatic potential in body fluids and tissue samples. The identification of these microRNA expression patterns could prove instrumental for the development of novel therapeutic molecules that either mimic or inhibit microRNA action. Additionally, an efficient delivery system mediated by viral vectors, nonviral carriers, or scaffold biomaterials is a prerequisite for implementing microRNA-based therapies; therefore, this review attempts to highlight essential microRNA molecules involved in the metastatic process of breast cancer and discuss recent advances in microRNA-based therapeutic approaches with potential future applications to the treatment sequence of breast cancer.
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Affiliation(s)
- Fahima Danesh Pouya
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Yousef Rasmi
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
- Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
| | - Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Eleni Zografos
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Mohadeseh Nemati
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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8
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Yu S, Zhou Y, Niu L, Qiao Y, Yan Y. Mesenchymal stem cell-derived exosome mir-342-3p inhibits metastasis and chemo-resistance of breast cancer through regulating ID4. Genes Genomics 2022; 44:539-550. [PMID: 35023068 DOI: 10.1007/s13258-021-01200-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 11/27/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND The mesenchymal stem cell-derived exosome (MSCs-exo) carrying microRNAs have been proved to regulate tumor biological activities. Clarifying molecular mechanism and identifying predictive microRNAs will be of great value in anti-tumor therapy improvement. OBJECTIVE We aimed to investigate the regulatory role of microRNA-342-3p (miR-342-3p) in MSCs-exo on breast cancer. METHODS Breast cancer tissues and cell lines were used to evaluate miR-342-3p expression in patients with or without lymph node/distal organ metastasis. The impact of MSCs-exo expression on tumor cell chemo-resistance and invasion/migration was measured. Dual-luciferase reporter gene assay was applied to identify binding site. Inhibitor of differentiation 4 (ID4) siRNA and miR-342-3p inhibitor transfection was conducted to further explore the miR-342-3p/ID4 axis on chemo-resistance and metastasis of breast cancer cells. RESULTS Breast cancer cells revealed significantly lower level of miR-342-3p in patients with metastatic diseases. miR-342-3p suppressed invasive and chemo-resistant behavior of breast cancer tumor cells. Binding site between miR-342-3p and ID4 was proved. ID4 could reverse the influence of miR-342-3p on chemo-resistance. The tumor inhibition effect of IDA siRNA in vivo was also identified. CONCLUSIONS This study demonstrated that miR-342-3p acted as potential tumor suppressor by inhibiting metastasis and chemo-resistance of breast cancer cells through targeting ID4. This study might provide potential therapy targets for the treatment of breast cancer.
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Affiliation(s)
- Shuyao Yu
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No.277, Yanta West Road, Shaanxi Province, 710061, Xi'an, China
| | - Yuhui Zhou
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No.277, Yanta West Road, Shaanxi Province, 710061, Xi'an, China
| | - Ligang Niu
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No.277, Yanta West Road, Shaanxi Province, 710061, Xi'an, China
| | - Yan Qiao
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No.277, Yanta West Road, Shaanxi Province, 710061, Xi'an, China
| | - Yu Yan
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No.277, Yanta West Road, Shaanxi Province, 710061, Xi'an, China.
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9
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Tommasi C, Pellegrino B, Boggiani D, Sikokis A, Michiara M, Uliana V, Bortesi B, Bonatti F, Mozzoni P, Pinelli S, Squadrilli A, Viani MV, Cassi D, Maglietta G, Meleti M, Musolino A. Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers. Front Oncol 2021; 11:700853. [PMID: 34552867 PMCID: PMC8450578 DOI: 10.3389/fonc.2021.700853] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 08/20/2021] [Indexed: 12/20/2022] Open
Abstract
Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.
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Affiliation(s)
- Chiara Tommasi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Benedetta Pellegrino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Daniela Boggiani
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Angelica Sikokis
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Maria Michiara
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Vera Uliana
- Medical Genetics Unit, University Hospital of Parma, Parma, Italy
| | - Beatrice Bortesi
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
| | - Francesco Bonatti
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Paola Mozzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Silvana Pinelli
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Anna Squadrilli
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
| | - Maria Vittoria Viani
- Dental School, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Diana Cassi
- Unit of Dentistry and Oral-Maxillo-Facial Surgery, Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Giuseppe Maglietta
- GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy.,Research and Innovation Unit, University Hospital of Parma, Parma, Italy
| | - Marco Meleti
- Dental School, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Antonino Musolino
- Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy.,Department of Medicine and Surgery, University of Parma, Parma, Italy.,GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica), Parma, Italy
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10
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Li X, Truong B, Xu T, Liu L, Li J, Le TD. Uncovering the roles of microRNAs/lncRNAs in characterising breast cancer subtypes and prognosis. BMC Bioinformatics 2021; 22:300. [PMID: 34082714 PMCID: PMC8176586 DOI: 10.1186/s12859-021-04215-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/20/2021] [Indexed: 12/30/2022] Open
Abstract
Background Accurate prognosis and identification of cancer subtypes at molecular level are important steps towards effective and personalised treatments of breast cancer. To this end, many computational methods have been developed to use gene (mRNA) expression data for breast cancer subtyping and prognosis. Meanwhile, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been extensively studied in the last 2 decades and their associations with breast cancer subtypes and prognosis have been evidenced. However, it is not clear whether using miRNA and/or lncRNA expression data helps improve the performance of gene expression based subtyping and prognosis methods, and this raises challenges as to how and when to use these data and methods in practice. Results In this paper, we conduct a comparative study of 35 methods, including 12 breast cancer subtyping methods and 23 breast cancer prognosis methods, on a collection of 19 independent breast cancer datasets. We aim to uncover the roles of miRNAs and lncRNAs in breast cancer subtyping and prognosis from the systematic comparison. In addition, we created an R package, CancerSubtypesPrognosis, including all the 35 methods to facilitate the reproducibility of the methods and streamline the evaluation. Conclusions The experimental results show that integrating miRNA expression data helps improve the performance of the mRNA-based cancer subtyping methods. However, miRNA signatures are not as good as mRNA signatures for breast cancer prognosis. In general, lncRNA expression data does not help improve the mRNA-based methods in both cancer subtyping and cancer prognosis. These results suggest that the prognostic roles of miRNA/lncRNA signatures in the improvement of breast cancer prognosis needs to be further verified. Supplementary Information The online version contains supplementary material available at 10.1186/s12859-021-04215-3.
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Affiliation(s)
- Xiaomei Li
- UniSA STEM, University of South Australia, Adelaide, Australia
| | - Buu Truong
- UniSA STEM, University of South Australia, Adelaide, Australia
| | - Taosheng Xu
- School of Life Sciences, University of Science and Technology, Hefei, China
| | - Lin Liu
- UniSA STEM, University of South Australia, Adelaide, Australia
| | - Jiuyong Li
- UniSA STEM, University of South Australia, Adelaide, Australia
| | - Thuc D Le
- UniSA STEM, University of South Australia, Adelaide, Australia. .,Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
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11
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Qiao EQ, Yang HJ, Zhang XP. Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis. J Zhejiang Univ Sci B 2021; 21:495-508. [PMID: 32478495 DOI: 10.1631/jzus.b1900584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.
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Affiliation(s)
- En-Qi Qiao
- Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China
| | - Hong-Jian Yang
- Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China
| | - Xi-Ping Zhang
- Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China
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12
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Circulating miRNAs as early indicators of diet and physical activity response in women with metastatic breast cancer. Future Sci OA 2021; 7:FSO694. [PMID: 33815828 PMCID: PMC8015665 DOI: 10.2144/fsoa-2020-0208] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Treatments for metastatic breast cancer (MBC) improve survival but often impose prolonged symptom burden. We performed molecular characterization of 84 miRNAs in the circulating serum of women with MBC to explore possible early indicators of intervention response. Expression levels of miR-10a-5p and miR-211-5p were downregulated in nonresponders, but upregulated in responders (miR-10a-5p: 0.40-fold and eightfold; miR 211-5p: 0.47-fold and fourfold). miR-205-5p expression was upregulated in both nonresponders and responders, but to a greater extent in responders (1.8-fold and sixfold). Additionally, levels of miR-10a-5p were negatively correlated with expression levels of IL-6 (r = -0.412). Exploration of these pathways may reveal mechanisms of action in lifestyle interventions aimed at improving quality of life and impacting disease progression for women with MBC. As treatment for women with metastatic breast cancer improves survival rates, interventions are needed that relieve symptom burden. We examined the serum of women with metastatic breast cancer who participated in a lifestyle intervention that improved diet and increased physical activity. Three miRNAs were discovered that may serve as early indicators of the ability of lifestyle interventions to improve quality of life and impact disease progression. Three miRNAs may predict how women with metastatic breast cancer respond to lifestyle interventions.
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13
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Abstract
Despite the decline in death rate from breast cancer and recent advances in targeted therapies and combinations for the treatment of metastatic disease, metastatic breast cancer remains the second leading cause of cancer-associated death in U.S. women. The invasion-metastasis cascade involves a number of steps and multitudes of proteins and signaling molecules. The pathways include invasion, intravasation, circulation, extravasation, infiltration into a distant site to form a metastatic niche, and micrometastasis formation in a new environment. Each of these processes is regulated by changes in gene expression. Noncoding RNAs including microRNAs (miRNAs) are involved in breast cancer tumorigenesis, progression, and metastasis by post-transcriptional regulation of target gene expression. miRNAs can stimulate oncogenesis (oncomiRs), inhibit tumor growth (tumor suppressors or miRsupps), and regulate gene targets in metastasis (metastamiRs). The goal of this review is to summarize some of the key miRNAs that regulate genes and pathways involved in metastatic breast cancer with an emphasis on estrogen receptor α (ERα+) breast cancer. We reviewed the identity, regulation, human breast tumor expression, and reported prognostic significance of miRNAs that have been documented to directly target key genes in pathways, including epithelial-to-mesenchymal transition (EMT) contributing to the metastatic cascade. We critically evaluated the evidence for metastamiRs and their targets and miRNA regulation of metastasis suppressor genes in breast cancer progression and metastasis. It is clear that our understanding of miRNA regulation of targets in metastasis is incomplete.
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Affiliation(s)
- Belinda J Petri
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40292, USA
| | - Carolyn M Klinge
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40292, USA.
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14
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miR-205 in Breast Cancer: State of the Art. Int J Mol Sci 2020; 22:ijms22010027. [PMID: 33375067 PMCID: PMC7792793 DOI: 10.3390/ijms22010027] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/11/2020] [Accepted: 12/17/2020] [Indexed: 12/18/2022] Open
Abstract
Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.
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15
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The Expression Patterns of BECN1, LAMP2, and PINK1 Genes in Colorectal Cancer Are Potentially Regulated by Micrornas and CpG Islands: An In Silico Study. J Clin Med 2020; 9:jcm9124020. [PMID: 33322704 PMCID: PMC7764710 DOI: 10.3390/jcm9124020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/06/2020] [Accepted: 12/10/2020] [Indexed: 12/15/2022] Open
Abstract
Background: Autophagy plays a dual role of tumor suppression and tumor promotion in colorectal cancer. The study aimed to find those microRNAs (miRNAs) important in BECN1, LAMP2, and PINK1 regulation and to determine the possible role of the epigenetic changes in examined colorectal cancer using an in silico approach. Methods: A total of 44 pairs of surgically removed tumors at clinical stages I‒IV and healthy samples (marginal tissues) from patients’ guts were analyzed. Analysis of the obtained results was conducted using the PL-Grid Infrastructure and Statistica 12.0 program. The miRNAs and CpG islands were estimated using the microrna.org database and MethPrimer program. Results: The autophagy-related genes were shown to be able to be regulated by miRNAs (BECN1—49 mRNA, LAMP2—62 mRNA, PINK1—6 mRNA). It was observed that promotion regions containing at least one CpG region were present in the sequence of each gene. Conclusions: The in silico analysis performed allowed us to determine the possible role of epigenetic mechanisms of regulation gene expression, which may be an interesting therapeutic target in the treatment of colorectal cancer.
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16
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Buocikova V, Rios-Mondragon I, Pilalis E, Chatziioannou A, Miklikova S, Mego M, Pajuste K, Rucins M, Yamani NE, Longhin EM, Sobolev A, Freixanet M, Puntes V, Plotniece A, Dusinska M, Cimpan MR, Gabelova A, Smolkova B. Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives. Cancers (Basel) 2020; 12:E3622. [PMID: 33287297 PMCID: PMC7761669 DOI: 10.3390/cancers12123622] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 11/30/2020] [Accepted: 11/30/2020] [Indexed: 12/12/2022] Open
Abstract
Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identification, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics.
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Affiliation(s)
- Verona Buocikova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia; (V.B.); (S.M.); (A.G.)
| | - Ivan Rios-Mondragon
- Department of Clinical Dentistry, University of Bergen, Aarstadveien 19, 5009 Bergen, Norway; (I.R.-M.); (M.R.C.)
| | - Eleftherios Pilalis
- e-NIOS Applications Private Company, Alexandrou Pantou 25, 17671 Kallithea, Greece; (E.P.); (A.C.)
- Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
| | - Aristotelis Chatziioannou
- e-NIOS Applications Private Company, Alexandrou Pantou 25, 17671 Kallithea, Greece; (E.P.); (A.C.)
- Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
| | - Svetlana Miklikova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia; (V.B.); (S.M.); (A.G.)
| | - Michal Mego
- 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia;
| | - Karlis Pajuste
- Latvian Institute of Organic Synthesis, Aizkraukles str. 21, LV-1006 Riga, Latvia; (K.P.); (M.R.); (A.S.); (A.P.)
| | - Martins Rucins
- Latvian Institute of Organic Synthesis, Aizkraukles str. 21, LV-1006 Riga, Latvia; (K.P.); (M.R.); (A.S.); (A.P.)
| | - Naouale El Yamani
- Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway; (N.E.Y.); (E.M.L.); (M.D.)
| | - Eleonora Marta Longhin
- Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway; (N.E.Y.); (E.M.L.); (M.D.)
| | - Arkadij Sobolev
- Latvian Institute of Organic Synthesis, Aizkraukles str. 21, LV-1006 Riga, Latvia; (K.P.); (M.R.); (A.S.); (A.P.)
| | - Muriel Freixanet
- Vall d Hebron, Institut de Recerca (VHIR), 08035 Barcelona, Spain; (M.F.); (V.P.)
| | - Victor Puntes
- Vall d Hebron, Institut de Recerca (VHIR), 08035 Barcelona, Spain; (M.F.); (V.P.)
- Institut Català de Nanosciència i Nanotecnologia (ICN2), Bellaterra, 08193 Barcelona, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
| | - Aiva Plotniece
- Latvian Institute of Organic Synthesis, Aizkraukles str. 21, LV-1006 Riga, Latvia; (K.P.); (M.R.); (A.S.); (A.P.)
| | - Maria Dusinska
- Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway; (N.E.Y.); (E.M.L.); (M.D.)
| | - Mihaela Roxana Cimpan
- Department of Clinical Dentistry, University of Bergen, Aarstadveien 19, 5009 Bergen, Norway; (I.R.-M.); (M.R.C.)
| | - Alena Gabelova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia; (V.B.); (S.M.); (A.G.)
| | - Bozena Smolkova
- Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia; (V.B.); (S.M.); (A.G.)
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17
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Wu Z, Tang H, Xiong Q, Liu D, Xia T, Liang H, Ye Q. Prognostic Role of microRNA-205 in Human Gynecological Cancer: A Meta-Analysis of Fourteen Studies. DNA Cell Biol 2020; 39:875-889. [PMID: 32354230 DOI: 10.1089/dna.2019.5316] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Several studies have revealed that miR-205 plays important roles in the development of gynecological cancers and thus may serve as a potential prognostic biomarker, but the current conclusions remain controversial. Therefore, the goal of this study was to explore the prognostic significance and functional mechanisms of miR-205 based on a meta-analysis and bioinformatics investigation. A total of 14 published studies containing 5835 patients were enrolled by searching the PubMed, EMBASE, and Cochrane library databases, 13 (14 datasets) and 5 (6 datasets) of which evaluated the correlations between the expression level of miR-205 and overall survival (OS) or disease-free survival (DFS)/disease-specific survival (DSS)/progression-free survival (PFS)/distant metastasis-free survival (DMFS), respectively. Furthermore, the use of online Kaplan-Meier plotter database analysis supplemented another seven results for OS. Then, a meta-analysis using these 21 and 6 datasets was performed. As a result, the overall analysis failed to demonstrate any significant associations between miR-205 expression and OS (p = 0.267) or DSS/DFS/DMFS/PFS (p = 0.457), but the subgroup analysis suggested that elevated miR-205 predicted a reduced OS for breast cancer (BC) patients (hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.72-0.98; p = 0.022), while higher miR-205 was associated with a poor DSS for endometrial cancer (EC) patients (HR = 2.19, 95% CI = 1.45-3.32; p < 0.001). Function prediction analysis indicated that miR-205 may be involved in BC by negatively influencing hub genes, SMARCA5 and SIAH1, whereas miR-205 may participate in EC by negatively modulating BMPR1B because of the presence of interactions of miR-205 with them at 3'-untranslated region and their opposite prognosis outcomes with miR-205. In conclusion, our findings suggest miR-205 may be a promising prognostic biomarker and therapeutic target for BC and EC patients.
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Affiliation(s)
- Zhixi Wu
- Department of Obstetrics and Gynecology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, China
| | - Hong Tang
- Department of Gynecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qian Xiong
- Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dong Liu
- Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Tingting Xia
- Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Huichao Liang
- Department of Obstetrics and Gynecology, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qingjian Ye
- Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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18
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Role of miR-21 as an authentic oncogene in mediating drug resistance in breast cancer. Gene 2020; 738:144453. [PMID: 32035242 DOI: 10.1016/j.gene.2020.144453] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Revised: 01/24/2020] [Accepted: 02/04/2020] [Indexed: 02/07/2023]
Abstract
Breast cancer (BC) is the most common cancer among women that is responsible for the most of the cancer-related death in worldwide. Drug resistance is remaining as a significant clinical obstacle to treat BC patients effectively. Therefore, to help overcome this problem, it is necessary to understand the mechanisms of drug resistance. microRNAs classify as highly conserved non-coding RNAs (~22 nucleotides) and interact with mRNAs-coding genes for direct post-transcriptional repression. It has been reported that miR-21 is overexpressed and also acts as oncomiR in many human malignancies by targeting of several tumor suppressor genes-associated with apoptosis, proliferation and metastasis. Specifically, it has been reported that miR-21 is responsible for the drug resistance and its overexpression is related to the development of Multi Drug Resistance (MDR) in breast cancer. In this review, we discussed about the role of miR-21 on the drug resistance of breast cancer.
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19
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Zografos E, Zagouri F, Kalapanida D, Zakopoulou R, Kyriazoglou A, Apostolidou K, Gazouli M, Dimopoulos MA. Prognostic role of microRNAs in breast cancer: A systematic review. Oncotarget 2019; 10:7156-7178. [PMID: 31903173 PMCID: PMC6935258 DOI: 10.18632/oncotarget.27327] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 10/26/2019] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRNAs) have been found to play an important role in breast cancer, functioning either as potential oncogenes or tumor suppressor genes, but their role in the prognosis of patients remains unclear. The aim of the present review study is to highlight recent preclinical and clinical studies performed on both circulating and tissue-specific miRNAs and their potential role as prognostic markers in breast cancer. We systematically searched the PubMed database to explore the prognostic value of miRNAs in breast cancer. After performing the literature search and review, 117 eligible studies were identified. We found that 110 aberrantly expressed miRNAs have been associated with prognosis in breast cancer. In conclusion, the collective data presented in this review indicate that miRNAs could serve as novel prognostic tools in breast cancer, while the clinical application of these findings has yet to be verified.
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Affiliation(s)
- Eleni Zografos
- Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Flora Zagouri
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Despoina Kalapanida
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Roubini Zakopoulou
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasios Kyriazoglou
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kleoniki Apostolidou
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Meletios-Athanasios Dimopoulos
- Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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20
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Abolghasemi M, Tehrani SS, Yousefi T, Karimian A, Mahmoodpoor A, Ghamari A, Jadidi-Niaragh F, Yousefi M, Kafil HS, Bastami M, Edalati M, Eyvazi S, Naghizadeh M, Targhazeh N, Yousefi B, Safa A, Majidinia M, Rameshknia V. MicroRNAs in breast cancer: Roles, functions, and mechanism of actions. J Cell Physiol 2019; 235:5008-5029. [PMID: 31724738 DOI: 10.1002/jcp.29396] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 09/30/2019] [Indexed: 12/13/2022]
Abstract
Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.
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Affiliation(s)
- Maryam Abolghasemi
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Sadra Samavarchi Tehrani
- Departmant of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Tooba Yousefi
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Ansar Karimian
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Ata Mahmoodpoor
- Anesthesiology Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aliakbar Ghamari
- Anesthesiology Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mehdi Yousefi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Bastami
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Edalati
- Department of Laboratory Sciences, Paramedical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shirin Eyvazi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Naghizadeh
- Departmant of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloufar Targhazeh
- Student Research Committee, Babol University Of Medical Sciences, Babol, Iran
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Safa
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
| | - Maryam Majidinia
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Vahid Rameshknia
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Faculty of Medicine, Islamic Azad University, Tabriz, Iran
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21
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Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel. Sci Rep 2019; 9:14913. [PMID: 31624308 PMCID: PMC6797767 DOI: 10.1038/s41598-019-51581-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 10/04/2019] [Indexed: 12/24/2022] Open
Abstract
MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656–1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517–1.000) and 10-years (AUC: 0.804. 95%CI: 0.517–1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.
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22
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Takeno T, Hasegawa T, Hasegawa H, Ueno Y, Hamataka R, Nakajima A, Okubo J, Sato K, Sakamaki T. MicroRNA-205-5p inhibits three-dimensional spheroid proliferation of ErbB2-overexpressing breast epithelial cells through direct targeting of CLCN3. PeerJ 2019; 7:e7799. [PMID: 31608175 PMCID: PMC6788438 DOI: 10.7717/peerj.7799] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 08/31/2019] [Indexed: 12/21/2022] Open
Abstract
We previously reported that microRNA-205-5p (miR-205-5p) is significantly decreased in the ErbB2-overexpressing breast epithelial cell line MCF10A-ErbB2 compared with control cells. In this study, we identified a direct target of miR-205-5p, chloride voltage-gated channel 3 (CLCN3). CLCN3 expression was induced by ErbB2 overexpression; this induced expression was then reduced to control levels by the transfection of the miR-205-5p precursor. In RNA-binding protein immunoprecipitation with Ago1/2/3 antibody, CLCN3 was significantly enriched in 293T embryonic kidney cells with miR-205-5p mimic transfection compared with negative control mimic transfection. In luciferase reporter assays using CLCN3 3'-UTR constructs, the miR-205-5p mimic significantly decreased reporter activity of both wild-type and partial mutant constructs in MCF10A-ErbB2 cells. In contrast, no inhibitory effects of the miR-205-5p mimic were detected using the complete mutant constructs. Since miR-205-5p expression in exosomes derived from MCF10A-neo cells was substantially higher than in exosomes derived from MCF10A-ErbB2 cells, we next investigated whether an exosome-mediated miR-205-5p transfer could control CLCN3 expression. To this end, exosomal miR-205-5p derived from MCF10A-neo cells was functionally transferred to MCF10A-ErbB2 cells, which served to decrease the expression of CLCN3. To assess the roles of CLCN3 in breast cancer, we next performed three-dimensional (3D) spheroid proliferation analyses using MCF10A-ErbB2 cells treated with MCF10A-neo-derived exosomes or CLCN3 shRNA stably expressing SKBR3 and MDA-MB-453 breast cancer cells. Our results showed that both treatment with MCF10A-neo-derived exosome and CLCN3 shRNA expression suppressed 3D spheroid proliferation. Collectively, these novel findings suggest that CLCN3 may be a novel direct target of miR-205-5p and this CLCN3/miR-205-5p interaction may serve a pivotal role in regulating breast cancer cellular proliferation under physiological conditions.
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Affiliation(s)
- Takayoshi Takeno
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Takuya Hasegawa
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Hiroki Hasegawa
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Yasuyuki Ueno
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Ryo Hamataka
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Aya Nakajima
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Junji Okubo
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Koji Sato
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
| | - Toshiyuki Sakamaki
- Laboratory of Public Health, Faculty of Pharmacy, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata, Japan
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23
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The Impact of Pre-analytical Factors on the Reliability of miRNA Measurements. CURRENT PATHOBIOLOGY REPORTS 2019. [DOI: 10.1007/s40139-019-00191-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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24
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Wang F, Zhang L, Xu H, Li R, Xu L, Qin Z, Zhong B. The Significance Role of microRNA-200c as a Prognostic Factor in Various Human Solid Malignant Neoplasms: A Meta-Analysis. J Cancer 2019; 10:277-286. [PMID: 30662548 PMCID: PMC6329861 DOI: 10.7150/jca.27536] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 08/19/2018] [Indexed: 12/11/2022] Open
Abstract
Objective: The aim of this study was to conduct a meta-analysis of 49 relevant studies to evaluate the prognostic value of miRNA-200c in various human malignant neoplasms. Methods: All relevant studies were identified by searching PubMed, Embase and Web of Science until August 15st, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of miRNA-200c for overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS) were calculated to investigate such associations. Results: Overall, 49 eligible studies were included in this meta-analysis. Our results showed that high expression of miRNA-200c was significantly correlated with a poor OS in cancer (pooled HR = 1.32, 95% CI: 1.06-1.65), but was not significantly correlated with PFS/RFS/DFS in cancer (pooled HR=1.05, 95% CI: 0.84-1.23). In our subgroup analysis, high miRNA-200c expression predicted a significantly worse OS (pooled HR = 1.50, 95% CI: 1.12-2.01) only in Caucasians. Moreover, high miRNA-200c expression even showed significantly poor OS (pooled HR = 1.88, 95% CI: 1.39-2.54) in blood samples. In addition, a significantly unfavorable OS (pooled HR = 2.69, 95% CI: 1.49-4.85) and (pooled HR = 2.66, 95% CI: 1.07-6.59) associated with up-regulated miRNA-200c expression were observed in breast cancer and endometrial cancer, respectively. Besides, high miRNA-200c expression also showed significantly poor PFS/RFS/DFS (pooled HR=1.66, 95% CI: 1.03-2.67) in breast cancer. Conclusions: Our findings indicated that high miRNA-200c expression was a promising biomarker for patient survival and disease progression in malignant tumors, especially in breast cancer and endometrial cancer. Considering the insufficient evidence, further large-scale researches and clinical studies were needed to verify these results.
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Affiliation(s)
- Feng Wang
- Department of Ultrasound, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, 210029, China
| | - Lei Zhang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Haoxiang Xu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Ran Li
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Lingyan Xu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Zhiqiang Qin
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
| | - Bing Zhong
- Department of Urology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, China.,Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
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25
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Jia W, Liang D, Li N, Liu M, Dong Z, Li J, Dong X, Yue Y, Hu P, Yao J, Zhao Q. Zebrafish microRNA miR-210-5p inhibits primitive myelopoiesis by silencing foxj1b and slc3a2a mRNAs downstream of gata4/5/6 transcription factor genes. J Biol Chem 2018; 294:2732-2743. [PMID: 30593510 DOI: 10.1074/jbc.ra118.005079] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 12/22/2018] [Indexed: 12/21/2022] Open
Abstract
Zebrafish gata4/5/6 genes encode transcription factors that lie on the apex of the regulatory hierarchy in primitive myelopoiesis. However, little is known about the roles of microRNAs in gata4/5/6-regulated processes. Performing RNA-Seq deep sequencing analysis of the expression changes of microRNAs in gata4/5/6-knockdown embryos, we identified miR-210-5p as a regulator of zebrafish primitive myelopoiesis. Knocking down gata4/5/6 (generating gata5/6 morphants) significantly increased miR-210-5p expression, whereas gata4/5/6 overexpression greatly reduced its expression. Consistent with inhibited primitive myelopoiesis in the gata5/6 morphants, miR-210-5p overexpression repressed primitive myelopoiesis, indicated by reduced numbers of granulocytes and macrophages. Moreover, knocking out miR-210 partially rescued the defective primitive myelopoiesis in zebrafish gata4/5/6-knockdown embryos. Furthermore, we show that the restrictive role of miR-210-5p in zebrafish primitive myelopoiesis is due to impaired differentiation of hemangioblast into myeloid progenitor cells. By comparing the set of genes with reduced expression levels in the gata5/6 morphants to the predicted target genes of miR-210-5p, we found that foxj1b and slc3a2a, encoding a forkhead box transcription factor and a solute carrier family 3 protein, respectively, are two direct downstream targets of miR-210-5p that mediate its inhibitory roles in zebrafish primitive myelopoiesis. In summary, our results reveal that miR-210-5p has an important role in the genetic network controlling zebrafish primitive myelopoiesis.
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Affiliation(s)
- Wenshuang Jia
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Dong Liang
- the Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, and
| | - Nan Li
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Meijing Liu
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Zhangji Dong
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Jingyun Li
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Xiaohua Dong
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Yunyun Yue
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061
| | - Ping Hu
- the Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, and
| | - Jihua Yao
- the State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
| | - Qingshun Zhao
- From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061,
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26
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Vahidian F, Mohammadi H, Ali-Hasanzadeh M, Derakhshani A, Mostaan M, Hemmatzadeh M, Baradaran B. MicroRNAs and breast cancer stem cells: Potential role in breast cancer therapy. J Cell Physiol 2018; 234:3294-3306. [PMID: 30362508 DOI: 10.1002/jcp.27246] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 07/24/2018] [Indexed: 12/19/2022]
Abstract
MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future.
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Affiliation(s)
- Fatemeh Vahidian
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Mohammadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Ali-Hasanzadeh
- Department of Immunology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Afshin Derakhshani
- Department of Immunology, Birjand University of Medical Sciences, Birjand, Iran.,Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Masoud Mostaan
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Islamic Azad university, Tabriz, Iran
| | - Maryam Hemmatzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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27
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Tan W, Yang M, Yang H, Zhou F, Shen W. Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers. Cancer Manag Res 2018; 10:4333-4347. [PMID: 30349367 PMCID: PMC6188192 DOI: 10.2147/cmar.s174435] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.
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Affiliation(s)
- Wenyong Tan
- Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, People's Republic of China, ;
- Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People Hospital), Jinan University, Shenzhen, People's Republic of China,
| | - Ming Yang
- Shenzhen Jingmai Medical Scientific and Technique Company, Shenzhen, People's Republic of China
| | - Hongli Yang
- Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People Hospital), Jinan University, Shenzhen, People's Republic of China,
| | - Fangbin Zhou
- Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People Hospital), Jinan University, Shenzhen, People's Republic of China,
| | - Weixi Shen
- Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, People's Republic of China, ;
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28
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Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: Past, present and future. Semin Cancer Biol 2018; 52:56-73. [DOI: 10.1016/j.semcancer.2017.08.010] [Citation(s) in RCA: 209] [Impact Index Per Article: 29.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 08/14/2017] [Accepted: 08/24/2017] [Indexed: 12/19/2022]
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29
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Zhang Y, Wang LJ, Yang HQ, Wang R, Wu HJ. MicroRNA-10b expression predicts long-term survival in patients with solid tumor. J Cell Physiol 2018; 234:1248-1256. [PMID: 30191959 DOI: 10.1002/jcp.27138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 07/09/2018] [Indexed: 01/23/2023]
Abstract
BACKGROUND Numerous studies have evaluated the significance of the microRNA-10b (miR-10b) in the development and progression of many cancers. Their findings revealed that increased expression of miR-10b is associated with unfavorable prognosis in patients with cancer. RESULTS A total of 1,834 patients from 19 studies were included in this study. A significantly shorter overall survival was observed in patients with increased expression of miR-10b (hazard ratio [HR] = 1.99, 95% confidence interval [CI]: 1.51-2.61). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cutoff value, analysis type, and sample size. Also, patients with a high expression level of miR-10b had a poorer disease-free survival rate (HR = 1.18, 95% CI: 1.05-1.33). In addition, the pooled odds ratios (ORs) showed that increased miR-10b was also associated with positive lymph node metastasis (OR = 2.09, 95% CI: 1.45-3.03), distant metastasis (OR = 2.40, 95% CI: 1.57-3.67), tumor size (OR = 3.86, 95% CI: 2.25-6.64), and poor clinical stage (OR = 5.02, 95% CI: 3.37-7.47). MATERIALS AND METHODS A systematic literature search was conducted on a number of electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Springer, Google Scholar, and Gene expression omnibus. We retrieved the relevant articles to examine the association between the miR-10b expression levels and patients' prognosis. The meta-analysis was conducted using the RevMan 5.2 software and Stata SE12.0 software. CONCLUSIONS High miR-10b expression was correlated with poor clinical outcome, which indicated the potential clinical use of miR-10b as a molecular biomarker for cancer, particularly in assessing prognosis for patients with cancers. Further studies should be performed to verify the clinical utility of miR-10b in human solid tumors.
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Affiliation(s)
- Yi Zhang
- Department of General Surgery, The First People's Hospital of Neijiang, Neijiang, Sichuan, China
| | - Li-Juan Wang
- Department of Nephrology, ShangRao People's Hospital, ShangRao, Jiangxi, China
| | - He-Quan Yang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Rong Wang
- Department of General Surgery, The First People's Hospital of Neijiang, Neijiang, Sichuan, China
| | - Hua-Jun Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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30
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Miao C, Zhang J, Zhao K, Liang C, Xu A, Zhu J, Wang Y, Hua Y, Tian Y, Liu S, Zhang C, Qin C, Wang Z. The significance of microRNA-148/152 family as a prognostic factor in multiple human malignancies: a meta-analysis. Oncotarget 2018; 8:43344-43355. [PMID: 28574848 PMCID: PMC5522150 DOI: 10.18632/oncotarget.17949] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 04/07/2017] [Indexed: 01/19/2023] Open
Abstract
Recent studies have demonstrated that microRNA-148/152 family emerges as a attractive biomarker for predicting tumor prognosis and progression. However, outcomes of different studies are controversial. Eligible Literature were searched through online databases: PubMed, EMBASE and Web of Science. A total of 24 eligible studies were ultimately enrolled in this meta-analysis. Results indicated that overexpression of miR-148/152 family was significantly correlated with enhanced overall/cause-specific survival (OS/CSS) (HR=0.63, 95% CI: 0.54-0.74). Stratified analysis indicated that high miR-148a and miR-148b expression predicted favorable OS/CSS (HR=0.76; 95% CI: 0.69-0.90) and (HR=0.49; 95% CI: 0.39-0.61), while miR-152 developed no significant impact (HR=0.40, 95% CI: 0.12-1.29). MiR-148/152 family was distinctly associated with superior OS/CSS in Asian (HR=0.53, 95% CI: 0.44-0.64), but not in Caucasian (HR=0.96, 95% CI: 0.82-1.13). Futhermore, miR-148/152 family expression also predicted longer disease/relapse/progression-free survival (DFS/RFS/PFS) (HR=0.37, 95% CI: 0.16-0.88). A significantly favorable DFS/RFS/PFS was observed in Asian (HR=0.21, 95% CI: 0.06-0.81) than that in Caucasian (HR=0.76, 95% CI: 0.31-1.87). miR-148/152 family overexpression also predicted longer DFS/RFS/PFS in tissues (HR=0.11, 95% CI: 0.01-0.98), but not in plasma/serum (HR=0.67, 95% CI: 0.38-1.18). Our meta-analysis demonstrated that overexpression of miR-148/152 predicted enhanced OS/CSS and DFS/RFS/PFS of cancer patients. MiR-148a/b family may serve as a potential prognostic factor in multiple human malignancies.
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Affiliation(s)
- Chenkui Miao
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianzhong Zhang
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Kai Zhao
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Liang
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Aiming Xu
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jundong Zhu
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuhao Wang
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yibo Hua
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ye Tian
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shouyong Liu
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Zhang
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Qin
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zengjun Wang
- State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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31
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Single-Step Incubation Determination of miRNAs in Cancer Cells Using an Amperometric Biosensor Based on Competitive Hybridization onto Magnetic Beads. SENSORS 2018; 18:s18030863. [PMID: 29543716 PMCID: PMC5877363 DOI: 10.3390/s18030863] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 03/07/2018] [Accepted: 03/12/2018] [Indexed: 12/20/2022]
Abstract
This work reports an amperometric biosensor for the determination of miRNA-21, a relevant oncogene. The methodology involves a competitive DNA-target miRNA hybridization assay performed on the surface of magnetic microbeads (MBs) and amperometric transduction at screen-printed carbon electrodes (SPCEs). The target miRNA competes with a synthetic fluorescein isothiocyanate (FITC)-modified miRNA with an identical sequence for hybridization with a biotinylated and complementary DNA probe (b-Cp) immobilized on the surface of streptavidin-modified MBs (b-Cp-MBs). Upon labeling, the FITC-modified miRNA attached to the MBs with horseradish peroxidase (HRP)-conjugated anti-FITC Fab fragments and magnetic capturing of the MBs onto the working electrode surface of SPCEs. The cathodic current measured at −0.20 V (versus the Ag pseudo-reference electrode) was demonstrated to be inversely proportional to the concentration of the target miRNA. This convenient biosensing method provided a linear range between 0.7 and 10.0 nM and a limit of detection (LOD) of 0.2 nM (5 fmol in 25 μL of sample) for the synthetic target miRNA without any amplification step. An acceptable selectivity towards single-base mismatched oligonucleotides, a high storage stability of the b-Cp-MBs, and usefulness for the accurate determination of miRNA-21 in raw total RNA (RNAt) extracted from breast cancer cells (MCF-7) were demonstrated.
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32
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Zouari M, Campuzano S, Pingarrón J, Raouafi N. Ultrasensitive determination of microribonucleic acids in cancer cells with nanostructured-disposable electrodes using the viral protein p19 for recognition of ribonucleic acid/microribonucleic acid homoduplexes. Electrochim Acta 2018. [DOI: 10.1016/j.electacta.2017.12.190] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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33
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Gurvits N, Autere TA, Repo H, Nykänen M, Kuopio T, Kronqvist P, Talvinen K. Proliferation-associated miRNAs-494, -205, -21 and -126 detected by in situ hybridization: expression and prognostic potential in breast carcinoma patients. J Cancer Res Clin Oncol 2018; 144:657-666. [PMID: 29362919 DOI: 10.1007/s00432-018-2586-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 01/16/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE To visualize by in situ hybridization (ISH) the levels of a set of proliferation-associated miRNAs and to evaluate their impact and clinical applicability in prognostication of invasive breast carcinoma. METHODS Tissue specimen from breast carcinoma patients were investigated for miRNAs-494, -205, -21 and -126. Prognostic associations for levels of miRNAs were analyzed based on complete clinical data and up to 22.5-year follow-up of the patient material (n = 285). For detection of the miRNAs, an automated sensitive protocol applying in situ hybridization was developed. RESULTS MiRNA-494 indicated prognostic value for patients with invasive breast carcinoma. Among node-negative disease reduced level of miRNA-494 predicted 8.5-fold risk of breast cancer death (p = 0.04). Altered levels and expression patterns of the studied miRNAs were observed in breast carcinomas as compared to benign breast tissue. CONCLUSIONS The present paper reports for the first time on the prognostic value of miRNA-494 in invasive breast cancer. Particularly, detection of miRNA-494 could benefit patients with node-negative breast cancer in identifying subgroups with aggressive disease. Based on our experience, the developed automatic ISH method to visualize altered levels of miRNAs-494, -205, -21 and -126 could be applied to routine pathology diagnostics providing that conditions of tissue treatment, especially fixation delays, are managed.
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Affiliation(s)
- Natalia Gurvits
- Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland.
| | - Tuomo-Artturi Autere
- Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland
| | - Heli Repo
- Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland
| | - Marjukka Nykänen
- Department of Pathology, Central Hospital of Central Finland, Jyväskylä, Finland
| | - Teijo Kuopio
- Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.,Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland
| | - Pauliina Kronqvist
- Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland
| | - Kati Talvinen
- Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland
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Pasculli B, Barbano R, Parrella P. Epigenetics of breast cancer: Biology and clinical implication in the era of precision medicine. Semin Cancer Biol 2018; 51:22-35. [PMID: 29339244 DOI: 10.1016/j.semcancer.2018.01.007] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 12/15/2017] [Accepted: 01/11/2018] [Indexed: 02/09/2023]
Abstract
In the last years, mortality from breast cancer has declined in western countries as a consequence of a more widespread screening resulting in earlier detection, as well as an improved molecular classification and advances in adjuvant treatment. Nevertheless, approximately one third of breast cancer patients will develop distant metastases and eventually die for the disease. There is now a compelling body of evidence suggesting that epigenetic modifications comprising DNA methylation and chromatin remodeling play a pivotal role since the early stages of breast cancerogenesis. In addition, recently, increasing emphasis is being placed on the property of ncRNAs to finely control gene expression at multiple levels by interacting with a wide array of molecules such that they might be designated as epigenetic modifiers. In this review, we summarize the current knowledge about the involvement of epigenetic modifications in breast cancer, and provide an overview of the significant association of epigenetic traits with the breast cancer clinicopathological features, emphasizing the potentiality of epigenetic marks to become biomarkers in the context of precision medicine.
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Affiliation(s)
- Barbara Pasculli
- Laboratory of Oncology, IRCCS "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy.
| | - Raffaela Barbano
- Laboratory of Oncology, IRCCS "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy.
| | - Paola Parrella
- Laboratory of Oncology, IRCCS "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy.
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Hironaka-Mitsuhashi A, Matsuzaki J, Takahashi RU, Yoshida M, Nezu Y, Yamamoto Y, Shiino S, Kinoshita T, Ushijima T, Hiraoka N, Shimizu C, Tamura K, Ochiya T. A tissue microRNA signature that predicts the prognosis of breast cancer in young women. PLoS One 2017; 12:e0187638. [PMID: 29141042 PMCID: PMC5687766 DOI: 10.1371/journal.pone.0187638] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 10/23/2017] [Indexed: 01/18/2023] Open
Abstract
Since breast cancers in young women are generally aggressive, young patients tend to be intensively treated with anti-cancer drugs. To optimize the strategy for treatment, particularly in young women, prognostic biomarkers are urgently required. The objective of this study was to identify a tissue microRNA (miRNA) signature that predicts prognosis in young breast cancer patients. Total RNA from 45 breast cancer patients aged <35 years was extracted from formalin-fixed paraffin-embedded (FFPE) tissues and analyzed using miRNA microarrays. Patients were categorized into two groups according to recurrence status within the 5 year period after surgery: recurrence (n = 11) and non-recurrent (n = 34). Histological parameters of hormone receptors and Ki-67 were statistically compared between the two groups. Differentially expressed miRNAs were identified, and their associations with overall survival (OS) were evaluated by log-rank test. The median observation period was 5.8 years for the recurrent group, and 9.1 years for the non-recurrent group. Nine miRNAs were significantly differentially expressed between the recurrent and non-recurrent groups. Receiver Operating Characteristic curve analysis was performed to evaluate the prediction accuracy of the identified miRNAs, and the resultant area under the curve was >0.7. Five of the miRNAs were validated by qRT-PCR, and the expression levels of three of those five (miR-183-5p, miR-194-5p, and miR-1285-5p), both alone and in combination, were associated with OS. In conclusion, we identified three candidate miRNAs that could be used separately or in combination as prognostic biomarkers in young breast cancer patients. This miRNA signature may enable selection of better treatment choices for young women with this disease.
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Affiliation(s)
- Ai Hironaka-Mitsuhashi
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
- Courses of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Ryou-u Takahashi
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Masayuki Yoshida
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
| | - Yutaka Nezu
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Yusuke Yamamoto
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Sho Shiino
- Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takayuki Kinoshita
- Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Toshikazu Ushijima
- Courses of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
- Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
| | - Chikako Shimizu
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kenji Tamura
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
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MicroRNA-10b and the clinical outcomes of various cancers: A systematic review and meta-analysis. Clin Chim Acta 2017; 474:14-22. [DOI: 10.1016/j.cca.2017.08.034] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 07/15/2017] [Accepted: 08/28/2017] [Indexed: 12/21/2022]
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Liu Y, Wang Y, Xu Q, Zhou X, Qin Z, Chen C, Zhang Q, Tian Y, Zhang C, Li X, Qin C. Prognostic evaluation of microRNA-210 in various carcinomas: Evidence from 19 studies. Medicine (Baltimore) 2017; 96:e8113. [PMID: 29068983 PMCID: PMC5671816 DOI: 10.1097/md.0000000000008113] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND We performed this meta-analysis to provide a comprehensive evaluation of the role of MicroRNA-210 (miR-210) expression on the overall survival (OS) rate of cancers. METHODS We searched for relevant available literatures on miR-210 and cancer until November 1st, 2016 on the databases PubMed, EMBASE, Cochrane Library, and Science Direct database. We calculated the pooled hazard ratio (HR) with 95% confidence intervals (CIs) for OS, which compared the high and low expression levels of miR-210 in patients of the available studies. Subgroup analysis was performed to evaluate the specific role of miR-210 in ethnicity and the type of cancers. Publication bias was evaluated using Begg funnel plots and Egger regression test. RESULTS Overall, 19 studies were involved in this meta-analysis. The result indicated that upregulated miR-210 might be associated with poor OS outcome in various carcinomas, with the pooled HR of 1.80 (95% CI: 1.29-2.51). When stratified by disease, significant results were detected in breast cancer (HR = 2.67, 95% CI: 1.24-5.76) and glioma (HR = 2.42, 95% CI: 1.32-4.43). Besides, in the subgroup analysis by ethnicity, significant results were detected only in Asian populations (HR = 2.14, 95% CI: 1.37-3.34). CONCLUSION The present meta-analysis suggests that high expressed miR-210 is significantly associated with OS in cancer patients, which has the potential to be a prognostic marker in cancers.
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Affiliation(s)
- Yincheng Liu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
- First Clinical Medical College of Nanjing Medical University
| | - Yichun Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Qitong Xu
- First Clinical Medical College of Nanjing Medical University
| | - Xiang Zhou
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Zhiqiang Qin
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Chen Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Qijie Zhang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Ye Tian
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Chao Zhang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
| | - Xiao Li
- Department of Urology, The affiliated Cancer Hospital of Jiangsu Province of Nanjing Medical University, Nanjing, China
| | - Chao Qin
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University
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Zouari M, Campuzano S, Pingarrón J, Raouafi N. Competitive RNA-RNA hybridization-based integrated nanostructured-disposable electrode for highly sensitive determination of miRNAs in cancer cells. Biosens Bioelectron 2017; 91:40-45. [DOI: 10.1016/j.bios.2016.12.033] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 12/09/2016] [Accepted: 12/12/2016] [Indexed: 11/30/2022]
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Qiu X, Zhu H, Liu S, Tao G, Jin J, Chu H, Wang M, Tong N, Gong W, Zhao Q, Qiang F, Zhang Z. Expression and prognostic value of microRNA-26a and microRNA-148a in gastric cancer. J Gastroenterol Hepatol 2017; 32:819-827. [PMID: 27529338 DOI: 10.1111/jgh.13533] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/10/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM In our previous study, we demonstrated that four microRNAs (miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non-invasive diagnostic biomarkers for gastric cancer (GC). METHODS We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan-Meier curves and log-rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis. RESULTS The median of miRNA expression in paraffin-embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down-regulation of miR-26a and miR-148a was significantly associated with shorter OS of GC patients either in the test set (miR-26a: P = 0.009; miR-148a: P = 0.005) or the validation set (miR-26a: P = 0.011; miR-148a: P = 0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR-26a and miR-148a were independent prognostic factors for predicting OS of patients with GC (miR-26a: HR = 0.76, 95% CI = 0.61-0.94; miR-148a: HR = 0.73, 95% CI = 0.58-0.91). Furthermore, elevated expression of miR-26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC-803 cells compared with negative control groups (P < 0.05). CONCLUSION These findings supported miR-26a and miR-148a could serve as potential prognostic biomarkers for GC.
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Affiliation(s)
- Xiaonan Qiu
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Haixia Zhu
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Core Laboratory, Nantong Tumor Hospital, Nantong, China
| | - Sang Liu
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Guoquan Tao
- Department of General Surgery, Huai-An First People's Hospital Affiliated to Nanjing Medical University, Huai-An, China
| | - Jing Jin
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Haiyan Chu
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Meilin Wang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Na Tong
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Weida Gong
- Department of General Surgery, Yixing Cancer Hospital, Yixing, China
| | - Qinghong Zhao
- Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fulin Qiang
- Core Laboratory, Nantong Tumor Hospital, Nantong, China
| | - Zhengdong Zhang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.,Department of Genetic Toxicology The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Stankevicins L, Barat A, Dessen P, Vassetzky Y, de Moura Gallo CV. The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model. PLoS One 2017; 12:e0173756. [PMID: 28346474 PMCID: PMC5367783 DOI: 10.1371/journal.pone.0173756] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 02/27/2017] [Indexed: 12/02/2022] Open
Abstract
MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness.
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Affiliation(s)
- L. Stankevicins
- Departamento de Genética, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, Brazil
- CNRS UMR 8126 «Signalisation, noyaux et innovations en cancérologie», Université Paris-Sud, Institut de Cancérologie Gustave-Roussy, Villejuif cedex, France
| | - A. Barat
- CNRS UMR 8126 «Signalisation, noyaux et innovations en cancérologie», Université Paris-Sud, Institut de Cancérologie Gustave-Roussy, Villejuif cedex, France
| | - P. Dessen
- Functional Genomics Unit, Institut de Cancérologie Gustave-Roussy, Villejuif, France
| | - Y. Vassetzky
- CNRS UMR 8126 «Signalisation, noyaux et innovations en cancérologie», Université Paris-Sud, Institut de Cancérologie Gustave-Roussy, Villejuif cedex, France
- N.K. Koltzov Institute of Developmental Biology RAS, Moscow, Russia
| | - C. V. de Moura Gallo
- Departamento de Genética, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, Brazil
- * E-mail:
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41
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Han SH, Kim HJ, Gwak JM, Kim M, Chung YR, Park SY. MicroRNA-222 Expression as a Predictive Marker for Tumor Progression in Hormone Receptor-Positive Breast Cancer. J Breast Cancer 2017; 20:35-44. [PMID: 28382093 PMCID: PMC5378578 DOI: 10.4048/jbc.2017.20.1.35] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 01/03/2017] [Indexed: 01/10/2023] Open
Abstract
Purpose The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. Results High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.
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Affiliation(s)
- Song-Hee Han
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Jeong Kim
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae Moon Gwak
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Mimi Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Yul Ri Chung
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - So Yeon Park
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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Bahrami A, Aledavood A, Anvari K, Hassanian SM, Maftouh M, Yaghobzade A, Salarzaee O, ShahidSales S, Avan A. The prognostic and therapeutic application of microRNAs in breast cancer: Tissue and circulating microRNAs. J Cell Physiol 2017; 233:774-786. [DOI: 10.1002/jcp.25813] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 01/19/2017] [Indexed: 12/14/2022]
Affiliation(s)
- Afsane Bahrami
- Molecular Medicine Group, Department of Modern Sciences and TechnologiesMashhad University of Medical SciencesMashhadIran
| | - Amir Aledavood
- Cancer Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Kazem Anvari
- Cancer Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Seyed Mahdi Hassanian
- Department of Medical Biotechnology, School of MedicineMashhad University of Medical SciencesMashhadIran
- Metabolic Syndrome Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Mina Maftouh
- Metabolic Syndrome Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
- Dr Akbarzadeh Pathobiology and Genetics LabMashhad University of Medical SciencesMashhadIran
| | - Ali Yaghobzade
- Student Research Committee, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Omid Salarzaee
- Student Research Committee, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Soodabeh ShahidSales
- Cancer Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
| | - Amir Avan
- Metabolic Syndrome Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
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Nassar FJ, Nasr R, Talhouk R. MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction. Pharmacol Ther 2016; 172:34-49. [PMID: 27916656 DOI: 10.1016/j.pharmthera.2016.11.012] [Citation(s) in RCA: 153] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results.
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Affiliation(s)
- Farah J Nassar
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
| | - Rabih Talhouk
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
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Dai H, Gallagher D, Schmitt S, Pessetto ZY, Fan F, Godwin AK, Tawfik O. Role of miR-139 as a surrogate marker for tumor aggression in breast cancer. Hum Pathol 2016; 61:68-77. [PMID: 27864119 DOI: 10.1016/j.humpath.2016.11.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 11/01/2016] [Accepted: 11/03/2016] [Indexed: 02/07/2023]
Abstract
MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.
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MESH Headings
- Biomarkers, Tumor/classification
- Biomarkers, Tumor/genetics
- Biopsy
- Breast Neoplasms/blood
- Breast Neoplasms/genetics
- Breast Neoplasms/mortality
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/blood
- Carcinoma, Ductal, Breast/genetics
- Carcinoma, Ductal, Breast/mortality
- Carcinoma, Ductal, Breast/pathology
- Cell Proliferation
- Disease Progression
- Down-Regulation
- Female
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Humans
- MicroRNAs/blood
- MicroRNAs/genetics
- Middle Aged
- Neoplasm Grading
- Neoplasm Invasiveness
- Phenotype
- Retrospective Studies
- Reverse Transcriptase Polymerase Chain Reaction
- Risk Factors
- Survival Analysis
- Tumor Burden
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Affiliation(s)
- Hongyan Dai
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Dan Gallagher
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Sarah Schmitt
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Ziyan Y Pessetto
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Fang Fan
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Andrew K Godwin
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
| | - Ossama Tawfik
- Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
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Amorim M, Salta S, Henrique R, Jerónimo C. Decoding the usefulness of non-coding RNAs as breast cancer markers. J Transl Med 2016; 14:265. [PMID: 27629831 PMCID: PMC5024523 DOI: 10.1186/s12967-016-1025-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 08/31/2016] [Indexed: 12/19/2022] Open
Abstract
Although important advances in the management of breast cancer (BC) have been recently accomplished, it still constitutes the leading cause of cancer death in women worldwide. BC is a heterogeneous and complex disease, making clinical prediction of outcome a very challenging task. In recent years, gene expression profiling emerged as a tool to assist in clinical decision, enabling the identification of genetic signatures that better predict prognosis and response to therapy. Nevertheless, translation to routine practice has been limited by economical and technical reasons and, thus, novel biomarkers, especially those requiring non-invasive or minimally invasive collection procedures, while retaining high sensitivity and specificity might represent a significant development in this field. An increasing amount of evidence demonstrates that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are aberrantly expressed in several cancers, including BC. miRNAs are of particular interest as new, easily accessible, cost-effective and non-invasive tools for precise management of BC patients because they circulate in bodily fluids (e.g., serum and plasma) in a very stable manner, enabling BC assessment and monitoring through liquid biopsies. This review focus on how ncRNAs have the potential to answer present clinical needs in the personalized management of patients with BC and comprehensively describes the state of the art on the role of ncRNAs in the diagnosis, prognosis and prediction of response to therapy in BC.
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Affiliation(s)
- Maria Amorim
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPOPorto), Research Center-LAB 3, F Bdg, 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.,Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal
| | - Sofia Salta
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPOPorto), Research Center-LAB 3, F Bdg, 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.,Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal
| | - Rui Henrique
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPOPorto), Research Center-LAB 3, F Bdg, 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.,Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.,Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal
| | - Carmen Jerónimo
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPOPorto), Research Center-LAB 3, F Bdg, 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. .,Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal.
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Jinling W, Sijing S, Jie Z, Guinian W. Prognostic value of circulating microRNA-21 for breast cancer: a systematic review and meta-analysis. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2016; 45:1-6. [PMID: 27684463 DOI: 10.1080/21691401.2016.1216856] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND There is an urgent need for novel noninvasive prognostic molecular tumor marker for monitoring the recurrence of breast cancer. MicroRNA-21 (miR-21) play a crucial role in the progression and aggressiveness of breast cancer, but its prognostic significance for patients with breast cancer remains inconclusive. The aim of this meta-analysis is to summarize the role of circulating miR-21 as a molecular marker in patients with breast cancer. MATERIAL AND METHODS Eligible studies were searched from the PubMed, EMBASE and Web of Science databases. The χ2 and I2 tests were used to evaluate heterogeneity between studies. The pooled hazard ratios (HR) with 95% confidence interval (CI) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied. The meta-analysis was conducted using the Review Manager 5 software. RESULTS A total of 7 articles which included 1629 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 1.51, 95%CI 1.15-1.98, p = 0.003). The subgroup analysis consisted of in tissue sample (HR = 1.66, 95%CI 1.03-2.67, p = 0.04) and serum sample (HR = 1.73, 95%CI 1.22-2.46, p = 0.002). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 2.36, 95%CI 1.04-4.78, p = 0.03). CONCLUSION Our findings suggest that the circulating miR-21 expression level can predict poor prognosis in patients with breast cancer.
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Affiliation(s)
- Wang Jinling
- a Department of Laboratory Medicine , the First Hospital of Zibo City , Shandong , China
| | - Sun Sijing
- b Department of Breast Surgery , the First Hospital of Zibo City , Shandong , China
| | - Zhang Jie
- c Department of Clinical Laboratory , Qilu Medical University , Shangdong , China
| | - Wang Guinian
- a Department of Laboratory Medicine , the First Hospital of Zibo City , Shandong , China
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47
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Markou A, Zavridou M, Sourvinou I, Yousef G, Kounelis S, Malamos N, Georgoulias V, Lianidou E. Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients. Clin Chem 2016; 62:1002-11. [DOI: 10.1373/clinchem.2015.253716] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 04/04/2016] [Indexed: 11/06/2022]
Abstract
Abstract
BACKGROUND
Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors.
METHODS
Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available.
RESULTS
In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P < 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR-210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231–7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals.
CONCLUSIONS
Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals.
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Affiliation(s)
- Athina Markou
- Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
| | - Martha Zavridou
- Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
| | - Ioanna Sourvinou
- Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
| | - George Yousef
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Sofia Kounelis
- Oncology Unit and Pathology Department, Helena Venizelou Hospital, Athens, Greece
| | - Nikos Malamos
- Oncology Unit and Pathology Department, Helena Venizelou Hospital, Athens, Greece
| | - Vasilis Georgoulias
- Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece
| | - Evi Lianidou
- Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece
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48
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Torrente-Rodríguez RM, Ruiz-Valdepeñas Montiel V, Campuzano S, Farchado-Dinia M, Barderas R, San Segundo-Acosta P, Montoya JJ, Pingarron JM. Fast Electrochemical miRNAs Determination in Cancer Cells and Tumor Tissues with Antibody-Functionalized Magnetic Microcarriers. ACS Sens 2016. [DOI: 10.1021/acssensors.6b00266] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | | | | | | | - Juan J. Montoya
- Canaan RI & Facultad Medicina, Universidad Alfonso X el Sabio, E-28691 Madrid, Spain
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Chen X, Hu H, He L, Yu X, Liu X, Zhong R, Shu M. A novel subtype classification and risk of breast cancer by histone modification profiling. Breast Cancer Res Treat 2016; 157:267-279. [DOI: 10.1007/s10549-016-3826-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 05/05/2016] [Indexed: 11/29/2022]
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50
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Huo L, Wang Y, Gong Y, Krishnamurthy S, Wang J, Diao L, Liu CG, Liu X, Lin F, Symmans WF, Wei W, Zhang X, Sun L, Alvarez RH, Ueno NT, Fouad TM, Harano K, Debeb BG, Wu Y, Reuben J, Cristofanilli M, Zuo Z. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer. Mod Pathol 2016; 29:330-46. [PMID: 26916073 PMCID: PMC11793840 DOI: 10.1038/modpathol.2016.38] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 01/09/2016] [Accepted: 01/09/2016] [Indexed: 02/07/2023]
Abstract
Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.
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Affiliation(s)
- Lei Huo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Yan Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Yun Gong
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Savitri Krishnamurthy
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Jing Wang
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Lixia Diao
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Chang-Gong Liu
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Xiuping Liu
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Feng Lin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - William F. Symmans
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Wei Wei
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Xinna Zhang
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Li Sun
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Ricardo H. Alvarez
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Naoto T. Ueno
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Tamer M. Fouad
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Kenichi Harano
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Bisrat G. Debeb
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - Yun Wu
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | - James Reuben
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
- Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
| | | | - Zhuang Zuo
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United State
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