Liquid Biopsy in Complex Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 18072

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Guest Editor
Azrieli Faculty of Medicine, Bar-Ilan University, Safad, Israel
Interests: experimental systems biology; genome and cancer biology; bioinformatics of complex diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is a leading cause of death in the world, and part of improving survival outcomes is early detection and personalized treatment. Assessment of molecular pathology is critical for cancer treatment, as tumor grade and metastatic potential determines therapeutic efficacy. Tissue-based analyses using tumor biopsies are limited by their availability and narrow scope of sampling (i.e., only one small section of a large, heterogeneous or metastatic tumor). Recent technology uses circulating tumor DNA, termed cell-free tumor DNA (ctDNA), which is present in body fluids such as blood plasma, urine, spinal fluid from dead cancer cells may help to assess the cancer type and grade. The advantage of liquid biopsies such as ctDNA is that we can look not only on the DNA or RNA coming from the cancer cells but also on the metagenome coming from the tumor micro-environment. In this Special Issue, we are looking for papers that discuss different aspects of liquid biopsy in complex diseases, including cancers, autoimmune-diseases and their microbiomes.

Dr. Milana Frenkel-Morgenstern
Guest Editor

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Keywords

  • liquid biopsy
  • cancers
  • complex diseases
  • cell-free DNA
  • circulating tumor DNA
  • micro-environment

Published Papers (6 papers)

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Research

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14 pages, 1424 KiB  
Article
Cell-Free DNA 5-Hydroxymethylcytosine Signatures for Lung Cancer Prognosis
by Jianming Shao, Randall J. Olsen, Saro Kasparian, Chuan He, Eric H. Bernicker and Zejuan Li
Cells 2024, 13(4), 298; https://doi.org/10.3390/cells13040298 - 06 Feb 2024
Viewed by 895
Abstract
Accurate prognostic markers are essential for guiding effective lung cancer treatment strategies. The level of 5-hydroxymethylcytosine (5hmC) in tissue is independently associated with overall survival (OS) in lung cancer patients. We explored the prognostic value of cell-free DNA (cfDNA) 5hmC through genome-wide analysis [...] Read more.
Accurate prognostic markers are essential for guiding effective lung cancer treatment strategies. The level of 5-hydroxymethylcytosine (5hmC) in tissue is independently associated with overall survival (OS) in lung cancer patients. We explored the prognostic value of cell-free DNA (cfDNA) 5hmC through genome-wide analysis of 5hmC in plasma samples from 97 lung cancer patients. In both training and validation sets, we discovered a cfDNA 5hmC signature significantly associated with OS in lung cancer patients. We built a 5hmC prognostic model and calculated the weighted predictive scores (wp-score) for each sample. Low wp-scores were significantly associated with longer OS compared to high wp-scores in the training [median 22.9 versus 8.2 months; p = 1.30 × 10−10; hazard ratio (HR) 0.04; 95% confidence interval (CI), 0.00–0.16] and validation (median 18.8 versus 5.2 months; p = 0.00059; HR 0.22; 95% CI: 0.09–0.57) sets. The 5hmC signature independently predicted prognosis and outperformed age, sex, smoking, and TNM stage for predicting lung cancer outcomes. Our findings reveal critical genes and signaling pathways with aberrant 5hmC levels, enhancing our understanding of lung cancer pathophysiology. The study underscores the potential of cfDNA 5hmC as a superior prognostic tool for guiding more personalized therapeutic strategies for lung cancer patients. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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19 pages, 34520 KiB  
Article
Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology
by Vasileios Vardas, Julia A. Ju, Athina Christopoulou, Anastasia Xagara, Vassilis Georgoulias, Athanasios Kotsakis, Catherine Alix-Panabières, Stuart S. Martin and Galatea Kallergi
Cells 2023, 12(15), 1940; https://doi.org/10.3390/cells12151940 - 26 Jul 2023
Cited by 2 | Viewed by 1514
Abstract
Metastasis, rather than the growth of the primary tumor, accounts for approximately 90% of breast cancer patient deaths. Microtentacles (McTNs) formation represents an important mechanism of metastasis. Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited targeted therapies. The present study [...] Read more.
Metastasis, rather than the growth of the primary tumor, accounts for approximately 90% of breast cancer patient deaths. Microtentacles (McTNs) formation represents an important mechanism of metastasis. Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited targeted therapies. The present study aimed to isolate viable circulating tumor cells (CTCs) and functionally analyze them in response to drug treatment. CTCs from 20 TNBC patients were isolated and maintained in culture for 5 days. Biomarker expression was identified by immunofluorescence staining and VyCap analysis. Vinorelbine-induced apoptosis was evaluated based on the detection of M30-positive cells. Our findings revealed that the CTC absolute number significantly increased using TetherChips analysis compared to the number of CTCs in patients’ cytospins (p = 0.006) providing enough tumor cells for drug evaluation. Vinorelbine treatment (1 h) on live CTCs led to a significant induction of apoptosis (p = 0.010). It also caused a significant reduction in Detyrosinated α-tubulin (GLU), programmed death ligand (PD-L1)-expressing CTCs (p < 0.001), and disruption of McTNs. In conclusion, this pilot study offers a useful protocol using TetherChip technology for functional analysis and evaluation of drug efficacy in live CTCs, providing important information for targeting metastatic dissemination at a patient-individualized level. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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20 pages, 4412 KiB  
Article
Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial
by Cheol-Kyu Park, Ha Ra Jun, Hyung-Joo Oh, Ji-Young Lee, Hyun-Ju Cho, Young-Chul Kim, Jeong Eun Lee, Seong Hoon Yoon, Chang Min Choi, Jae Cheol Lee, Sung Yong Lee, Shin Yup Lee, Sung-Min Chun and In-Jae Oh
Cells 2023, 12(9), 1246; https://doi.org/10.3390/cells12091246 - 25 Apr 2023
Cited by 3 | Viewed by 1517
Abstract
This study aimed to investigate the feasibility of blood-based biomarkers, including blood tumor mutation burden (bTMB), to predict atezolizumab efficacy in relapsed and advanced non-small cell lung cancer (NSCLC). Stage IV NSCLC patients who had previously received platinum-doublet chemotherapy were recruited and received [...] Read more.
This study aimed to investigate the feasibility of blood-based biomarkers, including blood tumor mutation burden (bTMB), to predict atezolizumab efficacy in relapsed and advanced non-small cell lung cancer (NSCLC). Stage IV NSCLC patients who had previously received platinum-doublet chemotherapy were recruited and received 1200 mg of atezolizumab every three weeks. Blood was collected to obtain plasma cell-free DNA (cfDNA) before the first cycle (C0) and at the fourth cycle (C4). bTMB was measured by CT-ULTRA in patients with cfDNA over 10 ng. The objective response rate (ORR) of the enrolled 100 patients was 10%, and there was no difference in ORR according to bTMB (cutoff: 11.5 muts/Mb) at C0 (high bTMB: 8.1% vs. low bTMB: 11.1%). However, the C4/C0 bTMB ratio was significantly lower in the durable clinical benefit (DCB) patients. The cfDNA concentration at C0, the C4/C0 ratio of the cfDNA concentration, the highest variant allele frequency (hVAF), and the VAF standard deviation (VAFSD) were significantly lower in the DCB patients. In the multivariate analysis, a high cfDNA concentration at C0 (cutoff: 8.6 ng/mL) and a C4/C0 bTMB ratio greater than 1 were significantly associated with progression-free survival. These results suggest that baseline levels and dynamic changes of blood-based biomarkers (bTMB, cfDNA concentration, and VAFSD) could predict atezolizumab efficacy in previously treated NSCLC patients. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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Review

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26 pages, 1128 KiB  
Review
A Comprehensive Review of the Potential Role of Liquid Biopsy as a Diagnostic, Prognostic, and Predictive Biomarker in Pancreatic Ductal Adenocarcinoma
by Kosta Stosic, Oier Azurmendi Senar, Jawad Tarfouss, Christelle Bouchart, Julie Navez, Jean-Luc Van Laethem and Tatjana Arsenijevic
Cells 2024, 13(1), 3; https://doi.org/10.3390/cells13010003 - 19 Dec 2023
Cited by 1 | Viewed by 1141
Abstract
Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at [...] Read more.
Pancreatic ductal adenocarcinoma is one of the most lethal malignant diseases, with a mortality rate being close to incidence. Due to its heterogeneity and plasticity, as well as the lack of distinct symptoms in the early phases, it is very often diagnosed at an advanced stage, resulting in poor prognosis. Traditional tissue biopsies remain the gold standard for making a diagnosis, but have an obvious disadvantage in their inapplicability for frequent sampling. Blood-based biopsies represent a non-invasive method which potentially offers easy and repeated sampling, leading to the early detection and real-time monitoring of the disease and hopefully an accurate prognosis. Given the urgent need for a reliable biomarker that can estimate a patient’s condition and response to an assigned treatment, blood-based biopsies are emerging as a potential new tool for improving patients’ survival and surveillance. In this article, we discuss the current advances and challenges in using liquid biopsies for pancreatic cancer, focusing on circulating tumour DNA (ctDNA), extracellular vesicles (EVs), and circulating tumour cells (CTCs), and compare the performance and reliability of different biomarkers and combinations of biomarkers. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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41 pages, 1353 KiB  
Review
Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests
by Tiago Brito-Rocha, Vera Constâncio, Rui Henrique and Carmen Jerónimo
Cells 2023, 12(6), 935; https://doi.org/10.3390/cells12060935 - 18 Mar 2023
Cited by 14 | Viewed by 9211
Abstract
Cancer remains a leading cause of death worldwide, partly owing to late detection which entails limited and often ineffective therapeutic options. Most cancers lack validated screening procedures, and the ones available disclose several drawbacks, leading to low patient compliance and unnecessary workups, adding [...] Read more.
Cancer remains a leading cause of death worldwide, partly owing to late detection which entails limited and often ineffective therapeutic options. Most cancers lack validated screening procedures, and the ones available disclose several drawbacks, leading to low patient compliance and unnecessary workups, adding up the costs to healthcare systems. Hence, there is a great need for innovative, accurate, and minimally invasive tools for early cancer detection. In recent years, multi-cancer early detection (MCED) tests emerged as a promising screening tool, combining molecular analysis of tumor-related markers present in body fluids with artificial intelligence to simultaneously detect a variety of cancers and further discriminate the underlying cancer type. Herein, we aim to provide a highlight of the variety of strategies currently under development concerning MCED, as well as the major factors which are preventing clinical implementation. Although MCED tests depict great potential for clinical application, large-scale clinical validation studies are still lacking. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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27 pages, 1329 KiB  
Review
Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives
by Diana Galoș, Alecsandra Gorzo, Ovidiu Balacescu and Daniel Sur
Cells 2022, 11(21), 3493; https://doi.org/10.3390/cells11213493 - 04 Nov 2022
Cited by 6 | Viewed by 2700
Abstract
Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current [...] Read more.
Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy. Full article
(This article belongs to the Special Issue Liquid Biopsy in Complex Diseases)
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