Abstract

Simple SummaryTo improve clinical outcomes, early diagnosis is mandatory in cancer patients. Several diagnostic approaches have been proposed, however, the main drawback relies on the invasive procedures required. Extracellular vesicles (EVs) are bilayer lipid membrane structures released by almost all cells and transferred to remote sites via the bloodstream. The observation that their cargo reflects the cell of origin has opened a new frontier for non-invasive biomarker discovery in oncology. Moreover, since EVs can be recovered from different body fluids, their impact as a Correctdiagnostic tool has gained particular interest. Hence, in the last decade, several studies using different biological fluids have been performed, showing the valuable contributions of EVs as tumour biomarkers, and their improved diagnostic power when combined with currently available tumour markers. In this review, the most relevant data on the diagnostic relevance of EVs, alone or in combination with the well-established tumour markers, are discussed.Early diagnosis, along with innovative treatment options, are crucial to increase the overall survival of cancer patients. In the last decade, extracellular vesicles (EVs) have gained great interest in biomarker discovery. EVs are bilayer lipid membrane limited structures, released by almost all cell types, including cancer cells. The EV cargo, which consists of RNAs, proteins, DNA, and lipids, directly mirrors the cells of origin. EVs can be recovered from several body fluids, including blood, cerebral spinal fluid (CSF), saliva, and Broncho-Alveolar Lavage Fluid (BALF), by non-invasive or minimally invasive approaches, and are therefore proposed as feasible cancer diagnostic tools. In this review, methodologies for EV isolation and characterization and their impact as diagnostics for the central nervous system, head and neck, lung, and gastrointestinal cancers are outlined. For each of these tumours, recent data on the potential clinical applications of the EV’s unique cargo, alone or in combination with currently available tumour biomarkers, have been deeply discussed.

Highlights

  • According to the World Health Organization (WHO), cancer represents the second cause of overall mortality worldwide and accounts for the highest clinical, social, and economic burden across all human diseases [1]

  • Wang et al [63] focused on nonfunctional pituitary adenomas (NFPAs) and demonstrated a lower expressions of folate receptor 1 (FOLR1) and epithelial cell adhesion molecules (EpCAM) in serum extracellular vesicles (EVs) derived from 10 patients suffering from invasive NFPAs compared to 10 healthy controls

  • Liu et al [97] have demonstrated the overexpression of cyclophilin A (CYPA) in sera, tissues, and circulating EVs of patients suffering from nasopharyngeal cancers (NPCs)

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Summary

Introduction

According to the World Health Organization (WHO), cancer represents the second cause of overall mortality worldwide and accounts for the highest clinical, social, and economic burden across all human diseases [1]. Liquid biopsy refers to the detection of cancer cells and/or cancer cell products/derivatives in body fluids for diagnosis, monitoring, treatment efficacy, and prognosis [8]. The EV cargo frequently differs between tumour- and healthy-derived EVs. EVs can be recovered from several body fluids, and in particular from blood, urine, Broncho-Alveolar Lavage Fluid (BALF), ascites, and cerebrospinal fluid (CSF). EVs can be recovered from several body fluids, and in particular from blood, urine, Broncho-Alveolar Lavage Fluid (BALF), ascites, and cerebrospinal fluid (CSF) Most importantly, these fluids can be obtained using non-invasive or minimally invasive procedures, representing a relevant diagnostic tool (Figure 2). These fluids can be obtained using non-invasive or minimally invasive procedures, representing a relevant diagnostic tool (Figure 2) Given these peculiarities, EVs hold great potential as cancer biomarkers and diagnostics. Evidence on EVs, as principal and/or ancillary diagnostic biomarkers, in the most clinically relevant neoplastic diseases involving the CNS, head and neck, lung, and the gastrointestinal tract, are discussed

Isolation and Purification Methods for EV Clinical Application
Method UC
Method
Method PCR
Gliomas
Nasopharyngeal and Oropharyngeal Squamous Cell Carcinoma
Laryngeal Squamous Cell Carcinoma
Lung Cancers
Colorectal Cancer
Pancreatic Cancer
Hepatocellular Carcinoma
Findings
Conclusions
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