microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer
TL;DR: Four microRNAs were selected to perform a screening test to discriminate between lung adenocarcinoma and granuloma, and the screening test showed 97.5% sensitivity, 72.0% specificity, and area under the curve receiver operating characteristic of 90.8%.
About: This article is published in Journal of Thoracic Oncology.The article was published on 2013-09-01 and is currently open access. It has received 363 citations till now. The article focuses on the topics: Lung cancer & Mass screening.
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Journal Article•
9,185 citations
TL;DR: A review of the biophysical properties and physiological functions of extracellular vesicles, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics can be found in this paper.
Abstract: The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics.
925 citations
TL;DR: The history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges are discussed.
Abstract: Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.
613 citations
TL;DR: Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines and are of potential interest as noninvasive biomarkers of cancer.
Abstract: Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation.
511 citations
Cites background from "microRNAs derived from circulating ..."
...Multiple other studies have shown that exosomes isolated from plasma of patients with different cancers, including glioblastoma [140], lung cancer [141], breast carcinoma [142], have distinct miRNA profiles....
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University of Maryland, Baltimore1, University of California, Davis2, University of Turin3, Netherlands Cancer Institute4, Aix-Marseille University5, University of California, San Francisco6, Yale Cancer Center7, The Chinese University of Hong Kong8, Ben-Gurion University of the Negev9, Medical University of Vienna10, Florida International University11, Harvard University12, Princess Margaret Cancer Centre13, Brigham and Women's Hospital14, Genome Institute of Singapore15, Stanford University16, University of Texas MD Anderson Cancer Center17, Ohio State University18, Anschutz Medical Campus19
TL;DR: It is concluded that liquid biopsy approaches have significant potential to improve patient care, and immediate implementation in the clinic is justified in a number of therapeutic settings relevant to NSCLC.
462 citations
Cites background from "microRNAs derived from circulating ..."
...A panel of four exosomal miRNAs could diagnose lung cancer with 96% sensitivity and 60% specificity in a retrospective cohort of 30 people of whom 10 were patients with lung cancer.(113) These promising preliminary results are still far from the clinical application....
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References
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25 Oct 1999
TL;DR: This highly anticipated third edition of the most acclaimed work on data mining and machine learning will teach you everything you need to know about preparing inputs, interpreting outputs, evaluating results, and the algorithmic methods at the heart of successful data mining.
Abstract: Data Mining: Practical Machine Learning Tools and Techniques offers a thorough grounding in machine learning concepts as well as practical advice on applying machine learning tools and techniques in real-world data mining situations. This highly anticipated third edition of the most acclaimed work on data mining and machine learning will teach you everything you need to know about preparing inputs, interpreting outputs, evaluating results, and the algorithmic methods at the heart of successful data mining. Thorough updates reflect the technical changes and modernizations that have taken place in the field since the last edition, including new material on Data Transformations, Ensemble Learning, Massive Data Sets, Multi-instance Learning, plus a new version of the popular Weka machine learning software developed by the authors. Witten, Frank, and Hall include both tried-and-true techniques of today as well as methods at the leading edge of contemporary research. *Provides a thorough grounding in machine learning concepts as well as practical advice on applying the tools and techniques to your data mining projects *Offers concrete tips and techniques for performance improvement that work by transforming the input or output in machine learning methods *Includes downloadable Weka software toolkit, a collection of machine learning algorithms for data mining tasks-in an updated, interactive interface. Algorithms in toolkit cover: data pre-processing, classification, regression, clustering, association rules, visualization
20,196 citations
TL;DR: It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).
Abstract: Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
10,484 citations
"microRNAs derived from circulating ..." refers background in this paper
...Furthermore, it has been suggested that cells can produce specific microRNAs that respond to stimuli or messages from adjacent cells.(11) Tumor cells are a perfect illustration of this paradigm because they produce exosomes containing microRNAs completely different from those present in normal cells from which neoplastic cells originated....
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Journal Article•
9,185 citations
TL;DR: Screening with the use of low-dose CT reduces mortality from lung cancer, as compared with the radiography group, and the rate of death from any cause was reduced.
Abstract: Background The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. Methods From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. Results The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Conclusions Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).
7,710 citations
TL;DR: It is shown here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity and established the measurement of tumor-derived mi RNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
Abstract: Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (≈22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
7,296 citations