Diagnostics

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12 pages, 1297 KiB

Open AccessArticle

The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1

by Athina N. Markou, Stavroula Smilkou, Emilia Tsaroucha and Evi Lianidou

Diagnostics 2021, 11(7), 1160; https://doi.org/10.3390/diagnostics11071160 - 25 Jun 2021

Cited by 4 | Viewed by 3296

Abstract

The presence of contaminating gDNA in RNA preparations is a frequent cause of false positives in RT-PCR-based analysis. However, in some cases, this cannot be avoided, especially when there are no exons–intron junctions in the lncRNA sequences. Due to the lack of exons [...] Read more.

The presence of contaminating gDNA in RNA preparations is a frequent cause of false positives in RT-PCR-based analysis. However, in some cases, this cannot be avoided, especially when there are no exons–intron junctions in the lncRNA sequences. Due to the lack of exons in few of long noncoding RNAs (lncRNAs) and the lack of DNAse treatment step in most studies reported so far, serious questions are raised about the specificity of lncRNA detection and the potential of reporting false-positive results. We hypothesized that minute amounts of gDNA usually co-extracted with RNA could give false-positive signals since primers would specifically bind to gDNA due to the lack of junction. In the current study, we evaluated the effect of gDNA and other forms of DNA like extrachromosomal circular DNAs (eccDNAs) contamination and the importance of including a DNAse treatment step on lncRNAsexpression.As a model, we have chosen as one of the most widely studied lncRNAs in cancer namely MALAT1, which lacks exons. When we tested this hypothesis in plasma and primary tissue samples from NSCLC patients, our findings clearly indicated that results on MALAT1 expression are highly affected by the presence of DNA contamination and that the DNAse treatment step is absolutely necessary to avoid false positive results. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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18 pages, 4081 KiB

Open AccessArticle

Optimal Halbach Configuration for Flow-through Immunomagnetic CTC Enrichment

by Michiel Stevens, Peng Liu, Tom Niessink, Anouk Mentink, Leon Abelmann and Leon Terstappen

Diagnostics 2021, 11(6), 1020; https://doi.org/10.3390/diagnostics11061020 - 2 Jun 2021

Cited by 16 | Viewed by 3397

Abstract

Due to the low frequency of circulating tumor cells (CTC), the standard CellSearch method of enumeration and isolation using a single tube of blood is insufficient to measure treatment effects consistently, or to steer personalized therapy. Using diagnostic leukapheresis this sample size can [...] Read more.

Due to the low frequency of circulating tumor cells (CTC), the standard CellSearch method of enumeration and isolation using a single tube of blood is insufficient to measure treatment effects consistently, or to steer personalized therapy. Using diagnostic leukapheresis this sample size can be increased; however, this also calls for a suitable new method to process larger sample inputs. In order to achieve this, we have optimized the immunomagnetic enrichment process using a flow-through magnetophoretic system. An overview of the major forces involved in magnetophoretic separation is provided and the model used for optimizing the magnetic configuration in flow through immunomagnetic enrichment is presented. The optimal Halbach array element size was calculated and both optimal and non-optimal arrays were built and tested using anti-EpCAM ferrofluid in combination with cell lines of varying EpCAM antigen expression. Experimentally measured distributions of the magnetic moment of the cell lines used for comparison were combined with predicted recoveries and fit to the experimental data. Resulting predictions agree with measured data within measurement uncertainty. The presented method can be used not only to optimize magnetophoretic separation using a variety of flow configurations but could also be adapted to optimize other (static) magnetic separation techniques. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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13 pages, 766 KiB

Open AccessArticle

Comparing Metabolomics Profiles in Various Types of Liquid Biopsies among Screening Participants with and without Advanced Colorectal Neoplasms

by Vanessa Erben, Gernot Poschet, Petra Schrotz-King and Hermann Brenner

Diagnostics 2021, 11(3), 561; https://doi.org/10.3390/diagnostics11030561 - 20 Mar 2021

Cited by 15 | Viewed by 3550

Abstract

Analysis of metabolomics has been suggested as a promising approach for early detection of colorectal cancer and advanced adenomas. We investigated and compared the metabolomics profile in blood, stool, and urine samples of screening colonoscopy participants and aimed to evaluate differences in metabolite [...] Read more.

Analysis of metabolomics has been suggested as a promising approach for early detection of colorectal cancer and advanced adenomas. We investigated and compared the metabolomics profile in blood, stool, and urine samples of screening colonoscopy participants and aimed to evaluate differences in metabolite concentrations between people with advanced colorectal neoplasms and those without neoplasms. Various types of bio-samples (plasma, feces, and urine) from 400 participants of screening colonoscopy were investigated using the MxP^® Quant 500 kit (Biocrates, Innsbruck, Austria). We detected a broad range of metabolites in blood, stool, and urine samples (504, 331, and 131, respectively). Significant correlations were found between concentrations in blood and stool, blood and urine, and stool and urine for 93, 154, and 102 metabolites, of which 68 (73%), 126 (82%), and 39 (38%) were positive correlations. We found significant differences between participants with and without advanced colorectal neoplasms for concentrations of 123, 49, and 28 metabolites in blood, stool and urine samples, respectively. We detected mostly positive correlations between metabolite concentrations in blood samples and urine or stool samples, and mostly negative correlations between urine and stool samples. Differences between subjects with and without advanced colorectal neoplasms were found for metabolite concentrations in each of the three bio-fluids. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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15 pages, 1587 KiB

Open AccessArticle

RNA-Based CTC Analysis Provides Prognostic Information in Metastatic Breast Cancer

by Areti Strati, Michail Nikolaou, Vassilis Georgoulias and Evi S. Lianidou

Diagnostics 2021, 11(3), 513; https://doi.org/10.3390/diagnostics11030513 - 14 Mar 2021

Cited by 17 | Viewed by 3339

Abstract

In metastatic breast cancer (MBC) the molecular characterization of circulating tumor cells (CTCs) provides a unique tool to understand metastasis-biology and therapy-resistance. We evaluated the prognostic significance of gene expression in EpCAM⁽⁺⁾ CTCs in 46 MBC patients based on a long follow-up. [...] Read more.

In metastatic breast cancer (MBC) the molecular characterization of circulating tumor cells (CTCs) provides a unique tool to understand metastasis-biology and therapy-resistance. We evaluated the prognostic significance of gene expression in EpCAM⁽⁺⁾ CTCs in 46 MBC patients based on a long follow-up. We selected a panel consisting of stem cell markers (CD24, CD44, ALDH1), the mesenchymal marker TWIST1, receptors (ESR1, PGR, HER2, EGFR) and the epithelial marker CK-19. Singleplex RT-qPCR was used for TWIST1 and CK-19 and multiplex RT-qPCR for stem cell markers and receptors. A group of 19 healthy donors (HD) was used as control. Univariate (p = 0.001) and multivariate analysis (p = 0.002) revealed the prognostic value of combined gene expression of CK-19(+), CD44^high/CD24^low, ALDH1^high/CD24^low and HER2 over-expression for overall survival (OS). The Kaplan–Meier estimates of OS were significantly different in patients positive for CK-19 (p = 0.028), CD44^high/CD24^low (p = 0.002), ALDH1^high/CD24^low (p = 0.007) and HER2-positive (p = 0.022). Our results indicate that combined gene expression analysis in EpCAM⁽⁺⁾ CTCs provides prognostic information in MBC. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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10 pages, 748 KiB

Open AccessArticle

Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer

by Virgílio Souza e Silva, Emne Ali Abdallah, Angelo Borsarelli Carvalho de Brito, Alexcia Camila Braun, Milena Shizue Tariki, Celso Abdon Lopes de Mello, Vinicius Fernando Calsavara, Rachel Riechelmann and Ludmilla Thomé Domingos Chinen

Diagnostics 2021, 11(3), 502; https://doi.org/10.3390/diagnostics11030502 - 12 Mar 2021

Cited by 11 | Viewed by 2741

Abstract

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with [...] Read more.

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET^® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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11 pages, 2002 KiB

Open AccessArticle

Detection and Investigation of Extracellular Vesicles in Serum and Urine Supernatant of Prostate Cancer Patients

by Samanta Salvi, Erika Bandini, Silvia Carloni, Valentina Casadio, Michela Battistelli, Sara Salucci, Ilaria Erani, Emanuela Scarpi, Roberta Gunelli, Giacomo Cicchetti, Michele Guescini, Massimiliano Bonafè and Francesco Fabbri

Diagnostics 2021, 11(3), 466; https://doi.org/10.3390/diagnostics11030466 - 8 Mar 2021

Cited by 14 | Viewed by 3149

Abstract

Prostate Cancer (PCa) is one of the most frequently identified urological cancers. PCa patients are often over-diagnosed due to still not highly specific diagnostic methods. The need for more accurate diagnostic tools to prevent overestimated diagnosis and unnecessary treatment of patients with non-malignant [...] Read more.

Prostate Cancer (PCa) is one of the most frequently identified urological cancers. PCa patients are often over-diagnosed due to still not highly specific diagnostic methods. The need for more accurate diagnostic tools to prevent overestimated diagnosis and unnecessary treatment of patients with non-malignant conditions is clear, and new markers and methods are strongly desirable. Extracellular vesicles (EVs) hold great promises as liquid biopsy-based markers. Despite the biological and technical issues present in their detection and study, these particles can be found highly abundantly in the biofluid and encompass a wealth of macromolecules that have been reported to be related to many physiological and pathological processes, including cancer onset, metastasis spreading, and treatment resistance. The present study aims to perform a technical feasibility study to develop a new workflow for investigating EVs from several biological sources. Serum and urinary supernatant EVs of PCa, benign prostatic hyperplasia (BPH) patients, and healthy donors were isolated and investigated by a fast, easily performable, and cost-effective cytofluorimetric approach for a multiplex detection of 37 EV-antigens. We also observed significant alterations in serum and urinary supernatant EVs potentially related to BPH and PCa, suggesting a potential clinical application of this workflow. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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16 pages, 2183 KiB

Open AccessArticle

Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

by Maarten J. IJzerman, Jasper de Boer, Arun Azad, Koen Degeling, Joel Geoghegan, Chelsee Hewitt, Frédéric Hollande, Belinda Lee, Yat Ho To, Richard W. Tothill, Gavin Wright, Jeanne Tie and Sarah-Jane Dawson

Diagnostics 2021, 11(1), 103; https://doi.org/10.3390/diagnostics11010103 - 11 Jan 2021

Cited by 37 | Viewed by 7082

Abstract

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. [...] Read more.

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts’ about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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12 pages, 1557 KiB

Open AccessArticle

The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease

by Christopher Boniface, Christopher Deig, Carol Halsey, Taylor Kelley, Michael B. Heskett, Charles R. Thomas, Jr., Paul T. Spellman and Nima Nabavizadeh

Diagnostics 2021, 11(1), 73; https://doi.org/10.3390/diagnostics11010073 - 5 Jan 2021

Cited by 11 | Viewed by 4078

Abstract

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility [...] Read more.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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14 pages, 1781 KiB

Open AccessArticle

Detection of EGFR Mutations in Plasma Cell-Free Tumor DNA of TKI-Treated Advanced-NSCLC Patients by Three Methodologies: Scorpion-ARMS, PNAClamp, and Digital PCR

by Annamaria Siggillino, Paola Ulivi, Luigi Pasini, Maria Sole Reda, Elisa Chiadini, Francesca Romana Tofanetti, Sara Baglivo, Giulio Metro, Lucio Crinó, Angelo Delmonte, Vincenzo Minotti, Fausto Roila and Vienna Ludovini

Diagnostics 2020, 10(12), 1062; https://doi.org/10.3390/diagnostics10121062 - 7 Dec 2020

Cited by 13 | Viewed by 3539

Abstract

Analysis of circulating cell-free tumor DNA (cftDNA) has emerged as a specific and sensitive blood-based approach to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. Still, there is some debate on what should be the [...] Read more.

Analysis of circulating cell-free tumor DNA (cftDNA) has emerged as a specific and sensitive blood-based approach to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. Still, there is some debate on what should be the preferential clinical method for plasma-derived cftDNA analysis. We tested 31 NSCLC patients treated with anti-EGFR tyrosine kinase inhibitors (TKIs), at baseline and serially during therapy, by comparing three methodologies in detecting EGFR mutations (L858R, exon 19 deletion, and T790M) from plasma: scorpions-amplification refractory mutation system (ARMS) methodology by using EGFR Plasma RGQ PCR Kit-QIAGEN, peptide nucleic acid (PNA) clamp and PANA RealTyper integration by using PNAClamp EGFR-PANAGENE, and digital real time PCR by using QuantStudio 3D Digital PCR System-Thermo Fisher Scientific. Specificity was 100% for all three mutations, independently from the platform used. The sensitivity for L858R (42.86%) and T790M (100%) did not change based on the method, while the sensitivity for Del 19 differed markedly (Scorpion-ARMS 45%, PNAClamp 75%, and Digital PCR 85%). The detection rate was also higher (94.23%) as measured by Digital PCR, and when we monitored the evolution of EGFR mutations over time, it evidenced the extreme inter-patient heterogeneity in terms of levels of circulating mutated copies. In our study, Digital PCR showed the best correlation with tissue biopsy and the highest sensitivity to attain the potential clinical utility of monitoring plasma levels of EGFR mutations. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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14 pages, 1134 KiB

Open AccessArticle

Limited Practical Utility of Liquid Biopsy in the Treated Patients with Advanced Breast Cancer

by Anna Niwinska, Aneta Bałabas, Maria Kulecka, Anna Kluska, Magdalena Piątkowska, Agnieszka Paziewska, Kazimiera Pyśniak, Wojciech Olszewski, Michał Mikula and Jerzy Ostrowski

Diagnostics 2020, 10(8), 523; https://doi.org/10.3390/diagnostics10080523 - 28 Jul 2020

Cited by 2 | Viewed by 2916

Abstract

Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected [...] Read more.

Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected from six healthy women and 37 patients with breast cancer (18 and 19 with stage III and IV tumors, respectively). CfDNA was assessed using the Oncomine Pan-Cancer Cell-Free Assay. In cfDNA samples from patients with BC, 1112 variants were identified, with only a few recurrent or hotspot mutations within specific regions of cancer genes. Of 65 potentially pathogenic variants detected in tumors, only 19 were also discovered in at least one blood sample. The allele frequencies of detected variants (VAFs) were <1% in cfDNA from all controls and patients with stage III BC, and 24/85 (28.2%) variants had VAFs > 1% in only 8 of 25 (32%) patients with stage IV BC. Copy number variations (CNVs) spanning CDK4, MET, FGFR1, FGFR2, ERBB2, MYC, and CCND3 were found in 1 of 12 (8%) and 8 of 25 (32%) patients with stage III and IV tumors, respectively. In healthy controls and patients without BC progression after treatment, VAFs were <1%, while in patients with metastatic disease and/or more advanced genomic alterations, VAFs > 1% and/or CNV were detected in approximately 30%. Therefore, most patients with stage IV BC could not be distinguished from those with stage III disease following therapy, based on liquid biopsy results. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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Review

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13 pages, 14113 KiB

Open AccessReview

Liquid Biopsy: A Family of Possible Diagnostic Tools

by Battistelli Michela

Diagnostics 2021, 11(8), 1391; https://doi.org/10.3390/diagnostics11081391 - 31 Jul 2021

Cited by 59 | Viewed by 5562

Abstract

Liquid biopsies could be considered an excellent diagnostic tool, in different physiological or pathological conditions. The possibility of using liquid biopsies for non-invasive clinical purposes is quite an old idea: indeed many years ago it was already being used in the field of [...] Read more.

Liquid biopsies could be considered an excellent diagnostic tool, in different physiological or pathological conditions. The possibility of using liquid biopsies for non-invasive clinical purposes is quite an old idea: indeed many years ago it was already being used in the field of non-invasive prenatal tests (NIPT) for autosomal fetal aneuploidy evaluation. In 1997 Lo et al. had identified fetal DNA in maternal plasma and serum, showing that about 10–15% of cfDNA in maternal plasma is derived from the placenta, and biologic fluid represents an important and non-invasive technique to evaluate state diseases and possible therapies. Nowadays, several body fluids, such as blood, urine, saliva and other patient samples, could be used as liquid biopsy for clinical non-invasive evaluation. These fluids contain numerous and various biomarkers and could be used for the evaluation of pathological and non-pathological conditions. In this review we will analyze the different types of liquid biopsy, their potential role in clinical diagnosis and the functional involvement of extracellular vesicles in these fluids as carriers. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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27 pages, 1070 KiB

Open AccessReview

Cell-Secreted Vesicles: Novel Opportunities in Cancer Diagnosis, Monitoring and Treatment

by Cristina Catoni, Veronica Di Paolo, Elisabetta Rossi, Luigi Quintieri and Rita Zamarchi

Diagnostics 2021, 11(6), 1118; https://doi.org/10.3390/diagnostics11061118 - 19 Jun 2021

Cited by 6 | Viewed by 3636

Abstract

Extracellular vesicles (EVs) are important mediators of intercellular communication playing a pivotal role in the regulation of physiological and pathological processes, including cancer. In particular, there is significant evidence suggesting that tumor-derived EVs exert an immunosuppressive activity during cancer progression, as well as [...] Read more.

Extracellular vesicles (EVs) are important mediators of intercellular communication playing a pivotal role in the regulation of physiological and pathological processes, including cancer. In particular, there is significant evidence suggesting that tumor-derived EVs exert an immunosuppressive activity during cancer progression, as well as stimulate tumor cell migration, angiogenesis, invasion and metastasis. The use of EVs as a liquid biopsy is currently a fast-growing area of research in medicine, with the potential to provide a step-change in the diagnosis and treatment of cancer, allowing the prediction of both therapy response and prognosis. EVs could be useful not only as biomarkers but also as drug delivery systems, and may represent a target for anticancer therapy. In this review, we attempted to summarize the current knowledge about the techniques used for the isolation of EVs and their roles in cancer biology, as liquid biopsy biomarkers and as therapeutic tools and targets. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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17 pages, 868 KiB

Open AccessReview

Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker

by Francis Yew Fu Tieng, Nadiah Abu, Learn-Han Lee and Nurul-Syakima Ab Mutalib

Diagnostics 2021, 11(3), 544; https://doi.org/10.3390/diagnostics11030544 - 18 Mar 2021

Cited by 21 | Viewed by 8885

Abstract

Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to [...] Read more.

Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay has historically been a tissue-based procedure that involves the testing of adequate tissue with a high concentration of cancer cells, in addition to the requirement for paired normal tissues. The invasive nature and specific prerequisite of such tests might hinder its application when surgery is not an option or when the tissues are insufficient. The application of next-generation sequencing, which is highly sensitive, in combination with liquid biopsy, therefore, presents an interesting possibility worth exploring. This review aimed to discuss the current body of evidence supporting the potential of liquid biopsy as a tool for MSI testing in CRC. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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Other

Jump to: Research, Review

7 pages, 245 KiB

Open AccessCase Report

Liquid Biopsy in Pediatric Renal Cancer: Stage I and Stage IV Cases Compared

by Elisabetta Rossi, Angelica Zin, Antonella Facchinetti, Cristina Poggiana, Lucia Tombolan, Maria Carmen Affinita, Paolo Bonvini, Luisa Santoro, Francesca Schiavi, Gianni Bisogno and Rita Zamarchi

Diagnostics 2020, 10(10), 810; https://doi.org/10.3390/diagnostics10100810 - 12 Oct 2020

Cited by 2 | Viewed by 2185

Abstract

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients’ follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in [...] Read more.

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients’ follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients’ outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design. Full article

(This article belongs to the Special Issue A Novel Class of Biomarkers: Novelties and Criticisms about Liquid Biopsy in Solid Tumors)

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