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Biomedicines
Special Issues
Liquid Biopsy in Diseases
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Liquid Biopsy in Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 12124

Special Issue Editors

Prof. Dr. Sehyun Shin

E-Mail Website
Guest Editor
1. School of Mechanical Engineering, College of Engineering, Korea University, 145 Anam-ro, Anam-dong, Seongbuk-gu, Seoul 136-701, Korea
2. Nano-Biofluignostic Engineering Research Center, Korea University, 145 Anam-ro, Anam-dong, Seongbuk-gu, Seoul 136-701, Korea
Interests: liquid biopsy; cfDNA; exosome; cancer; virus; RCA
Special Issues, Collections and Topics in MDPI journals
Dr. Kyong-Hwa Park

E-Mail Website
Guest Editor
Division of Oncology/Hematology, Department of Internal Medicine, Korea University, Seoul 02841, Republic of Korea
Interests: breast cancer; prostate cancer; ctDNA; exosome; NGS

Special Issue Information

Dear Colleagues,

In the age of precision medicine, tumor nucleic acid characterization plays an important role in providing patients with the most appropriate diagnosis and treatment. The advancements in PCR and next-generation sequencing (NGS) paved the way for personalized medicine by enabling the genetic characteristics of tumors to be evaluated. The development of blood-based liquid biopsy technology is also at the center of the development of precision medicine. In particular, liquid biopsy has emerged as the gold standard for diagnosis and treatment following its FDA approval in 2016.

We are inviting innovative and original research papers focused on the development of various technologies for cancer diagnosis and monitoring using liquid biopsy, focusing on the experimental/laboratory and pre-clinical medicine aspects. The submission of review articles describing the latest technology on this topic are also encouraged.

Focusing on liquid biopsy, this Special Issue covers the use of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), circulating tumor RNA (ctRNA), miRNA, and extracellular vesicles (EV).

Prof. Dr. Sehyun Shin
Dr. Kyong-Hwa Park
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liquid biopsy
  • ctDNA
  • exosomes
  • miRNA
  • CTCs
  • cancer

Published Papers (5 papers)

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Research

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17 pages, 2470 KiB  
Article
Liquid Biopsy Detecting Circulating Tumor Cells in Patients with Non-Small Cell Lung Cancer: Preliminary Results of a Pilot Study
by Maria Giovanna Mastromarino, Sara Parini, Danila Azzolina, Sara Habib, Marzia Luigia De Marni, Chiara Luise, Silvia Restelli, Guido Baietto, Elena Trisolini, Fabio Massera, Esther Papalia, Giulia Bora, Roberta Carbone, Caterina Casadio, Renzo Boldorini and Ottavio Rena
Biomedicines 2023, 11(1), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010153 - 07 Jan 2023
Cited by 1 | Viewed by 1787
Abstract
Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small [...] Read more.
Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients. We used Smart BioSurface® (SBS) slide, a nanoparticle-coated slide able to immobilize viable nucleated cellular fraction without pre-selection and preserve cell integrity. Forty patients undergoing lung resection for NSCLC were included; they were divided into two groups according to CTC value, with a cut-off of three CTCs/mL. All patients were positive for CTCs. The mean CTC value was 4.7(± 5.8 S.D.) per ml/blood. In one patient, next generation sequencing (NGS) analysis of CTCs revealed v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation, which has also been identified in tissue biopsy. CTCs count affected neither overall survival (OS, p = 0.74) nor progression-free survival (p = 0.829). Multivariable analysis confirmed age (p = 0.020) and pNodal-stage (p = 0.028) as negative predictors of OS. Preliminary results of this pilot study suggest the capability of this method in detecting CTCs in all early-stage NSCLC patients. NGS on single cell, identified as CTC by immunofluorescence staining, is a powerful tool for investigating the molecular landscape of cancer, with the aim of personalized therapies. Full article
(This article belongs to the Special Issue Liquid Biopsy in Diseases)
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11 pages, 2003 KiB  
Article
Multiplex Assay for Rapid Detection and Analysis of Nucleic Acid Using Barcode Receptor Encoded Particle (BREP)
by Semyung Jung, Ki Wan Bong and Wonhwi Na
Biomedicines 2022, 10(12), 3246; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123246 - 13 Dec 2022
Cited by 2 | Viewed by 1950
Abstract
Several multiplex nucleic acid assay platforms have been developed in response to the increasing importance of nucleic acid analysis, but these assays should be optimized as per the requirements of point-of-care for clinical diagnosis. To achieve rapid and accurate detection, involving a simple [...] Read more.
Several multiplex nucleic acid assay platforms have been developed in response to the increasing importance of nucleic acid analysis, but these assays should be optimized as per the requirements of point-of-care for clinical diagnosis. To achieve rapid and accurate detection, involving a simple procedure, we propose a new concept in the field of nucleic acid multiplex assay platforms using hydrogel microparticles, called barcode receptor-encoded particles (BREPs). The BREP assay detects multiple targets in a single reaction with a single fluorophore by analyzing graphically encoded hydrogel particles. By introducing sets of artificially synthesized barcode receptor and barcode probes, the BREP assay is easily applicable in multiplexing any genetic target; sets of barcode receptors and barcode probes should be designed delicately for universal application. The performance of the BREP assay was successfully verified in a multiplex assay for the identification of different malaria species with high sensitivity, wide dynamic range, fast detection time, and multiplexibility. Full article
(This article belongs to the Special Issue Liquid Biopsy in Diseases)
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18 pages, 822 KiB  
Article
Urinary Exosomal Cystatin C and Lipopolysaccharide Binding Protein as Biomarkers for Antibody−Mediated Rejection after Kidney Transplantation
by Mi Joung Kim, Seong Jun Lim, Youngmin Ko, Hye Eun Kwon, Joo Hee Jung, Hyunwook Kwon, Heounjeong Go, Yangsoon Park, Tae-Keun Kim, MinKyo Jung, Chan-Gi Pack, Young Hoon Kim, Kyunggon Kim and Sung Shin
Biomedicines 2022, 10(10), 2346; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102346 - 21 Sep 2022
Cited by 3 | Viewed by 1537
Abstract
We aimed to discover and validate urinary exosomal proteins as biomarkers for antibody−mediated rejection (ABMR) after kidney transplantation. Urine and for-cause biopsy samples from kidney transplant recipients were collected and categorized into the discovery cohort (n = 36) and a validation cohort [...] Read more.
We aimed to discover and validate urinary exosomal proteins as biomarkers for antibody−mediated rejection (ABMR) after kidney transplantation. Urine and for-cause biopsy samples from kidney transplant recipients were collected and categorized into the discovery cohort (n = 36) and a validation cohort (n = 65). Exosomes were isolated by stepwise ultra-centrifugation for proteomic analysis to discover biomarker candidates for ABMR (n = 12). Of 1820 exosomal proteins in the discovery cohort, four proteins were specifically associated with ABMR: cystatin C (CST3), serum paraoxonase/arylesterase 1, retinol-binding protein 4, and lipopolysaccharide−binding protein (LBP). In the validation cohort, the level of urinary exosomal LBP was significantly higher in the ABMR group (n = 25) compared with the T-cell-mediated rejection (TCMR) group and the no major abnormality (NOMOA) group. Urinary exosomal CST3 level was significantly higher in the ABMR group compared with the control and NOMOA groups. Immunohistochemical staining showed that LBP and CST3 in the glomerulus were more abundant in the ABMR group compared with other groups. The combined prediction probability of urinary exosomal LBP and CST3 was significantly correlated with summed LBP and CST3 intensity scores in the glomerulus and peritubular capillary as well as Banff g + ptc scores. Urinary exosomal CST3 and LBP could be potent biomarkers for ABMR after kidney transplantation. Full article
(This article belongs to the Special Issue Liquid Biopsy in Diseases)
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11 pages, 2081 KiB  
Article
Rapid and Efficient Extraction of Cell-Free DNA Using Homobifunctional Crosslinkers
by HyeonAh Seong, Junsoo Park, Minju Bae and Sehyun Shin
Biomedicines 2022, 10(8), 1883; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10081883 - 04 Aug 2022
Cited by 5 | Viewed by 2408
Abstract
Since its discovery in circulating blood seven decades ago, cell-free DNA (cfDNA) has become a highly focused subject in cancer management using liquid biopsy. Despite its clinical utility, the extraction of cfDNA from blood has many technical difficulties, including a low efficiency of [...] Read more.
Since its discovery in circulating blood seven decades ago, cell-free DNA (cfDNA) has become a highly focused subject in cancer management using liquid biopsy. Despite its clinical utility, the extraction of cfDNA from blood has many technical difficulties, including a low efficiency of recovery and long processing times. We introduced a magnetic bead-based cfDNA extraction method using homobifunctional crosslinkers, including dimethyl suberimidate dihydrochloride (DMS). Owing to its bifunctional nature, DMS can bind to DNA through either covalent or electrostatic bonding. By adopting amine-conjugated magnetic beads, DMS–DNA complexes can be rapidly isolated from blood plasma. Using standard washing and eluting processes, we successfully extracted cfDNA from plasma within 10 min. This method yielded a 56% higher extraction efficiency than that of a commercial product (QIAamp kit). Furthermore, the instant binding mechanism of amine coupling between the microbeads and DMS–DNA complexes significantly reduced the processing time. These results highlight the potential of this magnetic bead-based homobifunctional crosslinker platform for extraction of cfDNA from blood plasma. Full article
(This article belongs to the Special Issue Liquid Biopsy in Diseases)
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Review

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21 pages, 1919 KiB  
Review
Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management
by Sadia Hassan, Adeeb Shehzad, Shahid Ali Khan, Waheed Miran, Salman Khan and Young-Sup Lee
Biomedicines 2022, 10(8), 2047; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10082047 - 22 Aug 2022
Cited by 8 | Viewed by 3581
Abstract
Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances [...] Read more.
Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management. Full article
(This article belongs to the Special Issue Liquid Biopsy in Diseases)
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