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Molecular Cancer Feb 2022Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer... (Review)
Review
Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer diagnosis and prognosis prediction. Exosomes are a subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient cells and play a crucial role in mediating intercellular communication. Increasing studies suggest that exosomes have a great promise to serve as novel biomarkers in liquid biopsy, since large quantities of exosomes are enriched in body fluids and are involved in numerous physiological and pathological processes. However, the further clinical application of exosomes has been greatly restrained by the lack of high-quality separation and component analysis methods. This review aims to provide a comprehensive overview on the conventional and novel technologies for exosome isolation, characterization and content detection. Additionally, the roles of exosomes serving as potential biomarkers in liquid biopsy for the diagnosis, treatment monitoring, and prognosis prediction of cancer are summarized. Finally, the prospects and challenges of applying exosome-based liquid biopsy to precision medicine are evaluated.
Topics: Biomarkers, Tumor; Exosomes; Humans; Liquid Biopsy; Neoplasms; Precision Medicine; Prognosis
PubMed: 35180868
DOI: 10.1186/s12943-022-01509-9 -
Annual Review of Analytical Chemistry... Jun 2022Cancer remains one of the leading causes of death, and early detection of this disease is crucial for increasing survival rates. Although cancer can be diagnosed... (Review)
Review
Cancer remains one of the leading causes of death, and early detection of this disease is crucial for increasing survival rates. Although cancer can be diagnosed following tissue biopsy, the biopsy procedure is invasive; liquid biopsy provides an alternative that is more comfortable for the patient. While blood, urine, and cerebral spinal fluid can all be used as a source of liquid biopsy, saliva is an ideal source of body fluid that is readily available and easily collected in the most noninvasive manner. Characterization of salivary constituents in the disease setting provides critical data for understanding pathophysiology and the evaluation of diagnostic potential. The aim of saliva diagnostics is therefore to develop a rapid and noninvasive detection of oral and systemic diseases that could be used together with compact analysis systems in the clinic to facilitate point-of-care diagnostics.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Humans; Liquid Biopsy; Neoplasms; Saliva
PubMed: 35696523
DOI: 10.1146/annurev-anchem-061020-123959 -
Annals of Oncology : Official Journal... Apr 2021Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize... (Review)
Review
Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Exosomes; Humans; Liquid Biopsy; Male; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating
PubMed: 33548389
DOI: 10.1016/j.annonc.2021.01.074 -
Molecular Cancer May 2022Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early... (Review)
Review
Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.
Topics: Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Female; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Tumor Microenvironment
PubMed: 35538484
DOI: 10.1186/s12943-022-01577-x -
Nature Immunology Jul 2019Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease,...
Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
Topics: Biomarkers; Biopsy; Cluster Analysis; Computational Biology; Epithelial Cells; Flow Cytometry; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunophenotyping; Interferons; Kidney; Leukocytes; Lupus Nephritis; Lymphocytes; Molecular Sequence Annotation; Myeloid Cells; Single-Cell Analysis; Transcriptome
PubMed: 31209404
DOI: 10.1038/s41590-019-0398-x -
Cells Jul 2023The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues... (Review)
Review
The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, the surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumours, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.
Topics: Humans; Liquid Biopsy; Cell-Free Nucleic Acids; MicroRNAs; Central Nervous System Neoplasms; Biomarkers
PubMed: 37508574
DOI: 10.3390/cells12141911 -
International Journal of Molecular... Jan 2023Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a... (Review)
Review
Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy-techniques, molecules, and sample type-for lung cancer.
Topics: Humans; Early Detection of Cancer; Biomarkers, Tumor; Lung Neoplasms; Liquid Biopsy; Cell-Free Nucleic Acids
PubMed: 36768828
DOI: 10.3390/ijms24032505 -
Proceedings of the National Academy of... Sep 2019Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in...
Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type-specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na/K-ATPase, , mineralocorticoid receptor, and expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy.
Topics: Aged; Calcium; Diabetes Mellitus; Diabetic Nephropathies; Female; Gene Expression Profiling; Humans; Kidney; Kidney Glomerulus; Kidney Tubules, Distal; Kidney Tubules, Proximal; Magnesium; Male; Middle Aged; Potassium; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 31506348
DOI: 10.1073/pnas.1908706116 -
International Journal of Molecular... Sep 2022Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the... (Review)
Review
Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.
Topics: Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Female; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating
PubMed: 36077348
DOI: 10.3390/ijms23179952 -
International Journal of Molecular... Sep 2020Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of... (Review)
Review
Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Mitochondrial; Exosomes; Female; Fetus; Humans; Liquid Biopsy; MicroRNAs; Mutation; Precision Medicine; Pregnancy; Prognosis; RNA, Long Noncoding
PubMed: 32957662
DOI: 10.3390/ijms21186827