Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology

Valencia, Karmele; Montuenga, Luis M.

doi:10.3390/cancers13092147

Cited by 48 publications

(37 citation statements)

References 104 publications

(104 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to their multifactorial content, exosomes constitute a unique tool to capture the complexity and enormous heterogeneity of cancer in a longitudinal manner. Moreover, it is also due to molecular features like high nucleic acid concentrations and elevated coverage of genomic driver gene sequences [ 41 ]. Furthermore, recent studies developed by Lazar et al [ 42 ] highlighted the possible role of platelet-derived microvesicles, as previously demonstrated in the role of platelets in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Arance

Ramírez

Rubio-Roldán

et al. 2021

Cancers

View full text Add to dashboard Cite

Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

show abstract

Section: Discussionmentioning

confidence: 99%

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Arance

Ramírez

Rubio-Roldán

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Nevertheless, recent advances in patient organoid technology [ 51 ] have created additional utility for biopsy material, allowing the examination of personalized responses of the respective patient-derived organoids to chemotherapeutic agents and small-molecule inhibitor targets identified by molecular profiling. To this end, our data further suggest that for the initial diagnosis of PDAC and the molecular characterization of tumor DNA variants, fine-needle biopsies can so far not be replaced by liquid analytes with a similar high detection efficacy, yet actionable variant detection may be supported by a combination of easy-to-obtain cf- and evDNA since they are thought to more closely represent overall tumor heterogeneity [ 52 , 53 ]. To this end, additional variants were also observed in ev- and cfDNA in our study ( Figure 14 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Panel Sequencing of DNA Variants in cf-, ev- and tumorDNA for Pancreatic Ductal Adenocarcinoma Patients

Waldenmaier¹,

Schulte²,

Schönfelder³

et al. 2022

Cancers

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinomas (PDACs) are tumors with poor prognosis and limited treatment options. Personalized medicine aims at characterizing actionable DNA variants by next-generation sequencing, thereby improving treatment strategies and outcomes. Fine-needle tumor biopsies are currently the gold standard to acquire samples for DNA profiling. However, liquid biopsies have considerable advantages as they are minimally invasive and frequently obtainable and thus may help to monitor tumor evolution over time. However, which liquid analyte works best for this purpose is currently unclear. Our study aims to directly compare tumor-, circulating free (cf-) and extracellular vesicle-derived (ev)DNA by panel sequencing of matching patient material. We evaluated copy number variations (CNVs), single nucleotide variants (SNVs) and insertions and deletions (indels). Our data show that evDNA contains significantly larger DNA fragments up to 5.5 kb, in line with previous observations. Stringent bioinformatic processing revealed a significant advantage of evDNA with respect to cfDNA concerning detection performance for SNVs and a numerical increase for indels. A combination of ev- and cfDNA was clearly superior for SNV detection, as compared to either single analyte, thus potentially improving actionable variant prediction upon further optimization. Finally, calling of CNVs from liquid biopsies still remained challenging and uninformative.

show abstract

“…Our present observations therefore suggest that these differences in the AML protein-secretome are responsible for the differences in the AML effects on the MSC proteomic profiles between the two main patient clusters/subsets. However, it should be emphasized that cells can release proteins through their release of exosomes that also contain metabolites and μRNA [ 52 ]. These mediators may also contribute to the AML-associated modulation of MSC proteomic profiles.…”

Section: Discussionmentioning

confidence: 99%

Patient Heterogeneity in Acute Myeloid Leukemia: Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells

et al. 2021

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy, and non-leukemic stromal cells (including mesenchymal stem cells, MSCs) are involved in leukemogenesis and show AML-supporting effects. We investigated how constitutive extracellular mediator release by primary human AML cells alters proteomic profiles of normal bone marrow MSCs. An average of 6814 proteins (range 6493−6918 proteins) were quantified for 41 MSC cultures supplemented with AML-cell conditioned medium, whereas an average of 6715 proteins (range 6703−6722) were quantified for untreated control MSCs. The AML effect on global MSC proteomic profiles varied between patients. Hierarchical clustering analysis identified 10 patients (5/10 secondary AML) showing more extensive AML-effects on the MSC proteome, whereas the other 31 patients clustered together with the untreated control MSCs and showed less extensive AML-induced effects. These two patient subsets differed especially with regard to MSC levels of extracellular matrix and mitochondrial/metabolic regulatory proteins. Less than 10% of MSC proteins were significantly altered by the exposure to AML-conditioned media; 301 proteins could only be quantified after exposure to conditioned medium and 201 additional proteins were significantly altered compared with the levels in control samples (153 increased, 48 decreased). The AML-modulated MSC proteins formed several interacting networks mainly reflecting intracellular organellar structure/trafficking but also extracellular matrix/cytokine signaling, and a single small network reflecting altered DNA replication. Our results suggest that targeting of intracellular trafficking and/or intercellular communication is a possible therapeutic strategy in AML.

show abstract

Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology

Cited by 48 publications

References 104 publications

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Comparative Panel Sequencing of DNA Variants in cf-, ev- and tumorDNA for Pancreatic Ductal Adenocarcinoma Patients

Patient Heterogeneity in Acute Myeloid Leukemia: Leukemic Cell Communication by Release of Soluble Mediators and Its Effects on Mesenchymal Stem Cells

Contact Info

Product

Resources

About