Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment

Raimondi, Lavinia; Luca, Angela De; Costa, Viviana; Amodio, Nicola; Carina, Valeria; Bellavia, Daniele; Tassone, Pierfrancesco; Pagani, Stefania; Fini, Milena; Alessandro, Riccardo; Giavaresi, Gianluca

doi:10.18632/oncotarget.19852

Cited by 46 publications

(42 citation statements)

References 160 publications

(132 reference statements)

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“…A promising new approach to cancer diagnosis exploits circulating biomarkers that can be repeatedly and conveniently assessed with minimal complications. This is especially true of circulating exosomes, which contain a number of biomarkers specific to the originating cells . As a result, exosome analysis has garnered increasing attention owing to its novel features including the fact that exosomes function as reliable surrogates of parental cells and that they are both abundant and structurally stable.…”

Section: Discussionmentioning

confidence: 99%

Exosomes for Non‐Invasive Cancer Monitoring

Kalishwaralal

Kwon

Park

2018

Biotechnology Journal

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Exosomes, membrane‐bound phospholipid vesicles having diameters of 50–200 nm, are secreted by all cell types and circulate in human body fluids. These vesicles are known to carry cellular constituents that are specific to the originating cells (e.g., cytoplasmic/membrane proteins, RNA, and DNA). Thus, exosomes, which are both structurally stable and abundant, are robust indicators of cancers and, as a result, they have been utilized to monitor this disease in a manner that is less invasive than gold standard tissue biopsies. In this review, the history of exosomes and the specific biomarkers present in exosomes that enable accurate monitoring of various diseases are described. In addition, methods for analysis of exosomes and identification of biomarkers are presented with special emphasis being given to isolation and signaling strategies. Lastly, integrated, microfluidic systems developed for exosome‐based cancer diagnosis are described and future directions that research in this area will likely take are presented.

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Section: Discussionmentioning

confidence: 99%

Exosomes for Non‐Invasive Cancer Monitoring

Kalishwaralal

Kwon

Park

2018

Biotechnology Journal

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“…Several studies have examined c-miRNAs in OS [50], but few studies have been conducted in other sarcoma subtypes. Here, we used next generation sequencing to compare c-miRNA profiles of four sarcoma subtypes: OS, SS, ES, and GIST.…”

Section: Discussionmentioning

confidence: 99%

Signatures of circulating microRNA in four sarcoma subtypes

Koseła-Paterczyk¹,

Paziewska²,

Kulecka³

et al. 2020

J. Cancer

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Background: Sarcomas are rare malignant tumors of mesenchymal origin. The discovery of circulating biomarkers with high diagnostic value could supplement diagnosis of this heterogenous group of tumors. The aim of this study was to identify the profiles of circulating miRNA (c-miRNAs) in four groups of common bone and soft tissue sarcomas. Methods: At the time of diagnosis, blood samples were collected from 86 patients: 36 with locally advanced/unresectable/metastatic gastrointestinal stromal tumor (GIST) who received first-line treatment with imatinib; 16 with locally advanced osteosarcoma (OS); 26 with locally advanced synovial sarcoma (SS); and eight with locally advanced Ewing sarcoma (ES). In addition, samples were collected from 30 healthy controls. C-miRNAs were isolated using a miRCURY RNA Isolation Kit, followed by preparation of cDNA libraries and sequencing on the Ion Proton platform. Results: Pair-wise comparisons identified 156 unique c-miRNAs (adjusted P-value < 0.05) showing significant dysregulation between controls and patients; of these, 24, 36, 42, and 99 differentiated controls from pretherapeutic OS, SS, ES, and GIST, respectively. Ten c-miRNAs were commonly altered in at least three sarcoma types. Receiver operating characteristic curves and area under the curve (ROC-AUC) analyses revealed that a four-miRNA diagnostic classifier was able to differentiate controls from ES, GIST, OS, and SS, with AUC-ROC values of 1, 0.97, 0.95, and 0.94, respectively. Conclusions: Aberrant miRNA expression signatures were identified in serum from patients with four different sarcoma subtypes. Differences in miRNA expression profiles between sarcoma patients and healthy volunteers suggest that miRNAs may play a role in sarcoma development.

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“…Liquid biopsy may be highly advantageous, given the difficulty of recovering the bone sample for disease staging. In fact, it is a non-invasive and also time-saving approach; moreover, it may offer more precise and accurate information on early detection, therapeutic decisions, and response to therapy in OS [12,13].…”

Section: Discussionmentioning

confidence: 99%

Gathering Novel Circulating Exosomal microRNA in Osteosarcoma Cell Lines and Possible Implications for the Disease

Cuscino

Raimondi

Luca

et al. 2019

Cancers

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One of the goals of personalized medicine is to understand and treat diseases with greater precision through the molecular profile of the patient. This profiling is becoming a powerful tool for the discovery of novel biomarkers that can guide physicians in assessing, in advance, the disease stage, and monitoring disease progression. Circulating miRNAs and exosomal miRNAs, a group of small non-coding RNAs, are considered the gold standard diagnostic biomarkers for human diseases. We have previously demonstrated that osteosarcoma-derived exosomes are able to influence crucial mechanisms inside tumor niches, inducing osteoclast differentiation, and sustaining bone resorption activity. Here we discovered, through Next-Generation Sequencing (NGS), eight novel microRNAs in three different osteosarcoma cell lines, and assessed the selective packaging into the exosomes released. We then investigated, as proof-of-principle, the presence of the novel microRNAs in osteosarcoma patient samples, and found that 5 of the 8 novel microRNAs were more present in circulating exosomes of osteosarcoma patients compared with the controls. These results raise a question: Could the 8 novel microRNAs play a role for osteosarcoma pathogenesis? Although still premature, the results are encouraging, and further studies with a validation in a larger cohort are needed.

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Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment

Cited by 46 publications

References 160 publications

Exosomes for Non‐Invasive Cancer Monitoring

Exosomes for Non‐Invasive Cancer Monitoring

Signatures of circulating microRNA in four sarcoma subtypes

Gathering Novel Circulating Exosomal microRNA in Osteosarcoma Cell Lines and Possible Implications for the Disease

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