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Biomedicines
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Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention
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Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention

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

Deadline for manuscript submissions: 28 February 2026 | Viewed by 6500

Special Issue Editors

Dr. Mohamed Kamal

E-Mail Website
Guest Editor
Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA
Interests: cancer biology; metastasis; drug resistance; biomarkers; circulating tumor cells; cancer stem cells; liquid biopsy; early detection
Prof. Dr. James Hicks

E-Mail Website
Guest Editor
Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA
Interests: single-cell analysis; genomics; genetics; liquid biopsies

Special Issue Information

Dear Colleagues,

Liquid biopsy is a minimally invasive alternative to traditional tissue biopsies capable of providing longitudinal monitoring of tumor progression and response to therapy. Liquid biopsies such as blood, urine, aqueous humor, and ascites through the analyses of cell-free nucleic acids (cfDNA, cfRNA), circulating tumor cells (CTCs), and extracellular vehicles (EVs) have shown great promise in cancer diagnosis, prognosis, and treatment monitoring. Recent advancements in assay development and the integration of artificial intelligence (AI) have significantly enhanced the sensitivity and specificity of liquid biopsy techniques. In addition to their value as a minimally invasive tool for longitudinal monitoring of cancer, liquid biopsies could also serve as a rich source of information for a better understanding of cellular and molecular mechanisms of metastasis leading to the discovery of new drug targets and biomarkers. On top of that, recent reports have showed that elimination of CTCs from patients’ circulation could hinder metastasis.

This Special Issue aims to capture the current state of the art in liquid biopsy research including the following topics:

  1. Technological innovations including AI-assisted models for the detection of rare circulating events and for patients’ classification.
  2. Liquid biopsy-based biomarkers for predicting tumor prognosis and monitoring response to treatment.
  3. Liquid biopsy in cancer screening programs at the population level and of high-risk groups for early detection of cancer and detection of the disease’s precursors.
  4. Patient Risk Stratification using liquid biopsy biomarkers.
  5. Studies providing better understanding of the Biology of metastasis.
  6. Therapeutic interventions through the elimination of circulating cancer-related events.

Dr. Mohamed Kamal
Prof. Dr. James Hicks
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
  • biomarkers
  • circulating tumor cells

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Published Papers (4 papers)

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Research

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19 pages, 4559 KB  
Article
Genetic Variants and Soluble Isoforms of PD-1/PD-L1 as Novel Biomarkers for Pancreatic Ductal Adenocarcinoma (PDAC) Susceptibility and Prognosis
by Marwa Hassan, Walaa H. El-Maadawy, Yasmine Elhusseny, Fatma Elbatol Agamy, Sally A. Fahim and Mahmoud Balata
Biomedicines 2025, 13(9), 2246; https://doi.org/10.3390/biomedicines13092246 - 12 Sep 2025
Viewed by 599
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm often diagnosed at advanced stages. Immune checkpoint molecules, particularly programmed cell death protein-1 (PD-1) and its ligand PD-L1, are pivotal in tumor immune evasion. Genetic polymorphisms in PD-1/PD-L1 and their soluble isoforms (sPD-1/sPD-L1) [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm often diagnosed at advanced stages. Immune checkpoint molecules, particularly programmed cell death protein-1 (PD-1) and its ligand PD-L1, are pivotal in tumor immune evasion. Genetic polymorphisms in PD-1/PD-L1 and their soluble isoforms (sPD-1/sPD-L1) may influence individual susceptibility to cancer and disease progression. Therefore, this study was conducted to examine the correlation between PD-1/PD-L1 gene polymorphisms, serum levels of sPD-1/sPD-L1, and their association with PDAC susceptibility, severity, and prognostication. Methods: This case–control study was performed with 150 PDAC patients and 150 controls. Clinical and laboratory data, including tumor markers (CA19-9 and CEA), were recorded. Allele-specific PCR was utilized to genotype PD-1 (rs6749527 and rs7421861) and PD-L1 (rs2297136, and rs4143815). sPD-1/sPD-L1 were quantified with ELISA. Mapping of the Kaplan–Meier survival curve of mutant genes was performed. Results: The rs7421861 AG and GG and rs4143815 GG genotypes, together with their G-alleles, were linked to increased PDAC risk and greater tumor burden. In contrast, the rs2297136 GG genotype and G-allele conferred protection against PDAC development. Serum sPD-L1 levels, rather than sPD-1, were markedly elevated in PDAC patients, progressively increased with tumor grade, and correlated with tumor markers. Also, higher PD-L1 gene expression was associated with lower overall survival. Conclusions: PD-1/PD-L1 genetic variants, particularly rs7421861 and rs4143815, along with sPD-L1 levels, correlate with PDAC susceptibility and disease severity. These findings endorse the prospects of integrating immune checkpoint genetic variants and soluble biomarkers for early identification, risk stratification, prognostication, and personalized therapeutic strategies in PDAC management. Full article
(This article belongs to the Special Issue Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention)
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26 pages, 1442 KB  
Article
The Association of Toll-like Receptor-9 Gene Single-Nucleotide Polymorphism and AK155(IL-26) Serum Levels with Chronic Obstructive Pulmonary Disease Exacerbation Risk: A Case-Controlled Study with Bioinformatics Analysis
by Entsar R. Mokhtar, Salwa I. Elshennawy, Heba Elhakeem, Rayyh A. M. Saleh, Sawsan Bakr Elsawy, Khadiga S. M. Salama, Maha Fathy Mohamed, Rania Hamid Bahi, Hayam H. Mansour, Sammar Ahmed Kasim Mahmoud, Marwa M. Hassan, Sara M. Elhadad, Hanaa Mohammed Eid El Sayed, Aliaa N. Mohamed and Nadia M. Hamdy
Biomedicines 2025, 13(3), 613; https://doi.org/10.3390/biomedicines13030613 - 3 Mar 2025
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Abstract
Background: A crucial challenge is the determination of chronic obstructive pulmonary disease (COPD) immune-related mechanisms, where one of the important components of the inflammatory axes in COPD is Toll-like receptor-9 (TLR9) and interleukin-26 AK155(IL-26). Aim: To examine the relation between TLR9 (T1237C) SNP [...] Read more.
Background: A crucial challenge is the determination of chronic obstructive pulmonary disease (COPD) immune-related mechanisms, where one of the important components of the inflammatory axes in COPD is Toll-like receptor-9 (TLR9) and interleukin-26 AK155(IL-26). Aim: To examine the relation between TLR9 (T1237C) SNP rs5743836 and serum levels of AK155(IL-26) with the exacerbation of COPD. Subjects: A total of 96 COPD patients sub-classified into two groups. Materials: DNA was purified from blood samples of stable COPD patients (n = 48) vs. exacerbated COPD patients (n = 48) as well as 42 age- and sex-matched healthy smokers and passive smokers as a control group. Methods: Genotyping for TLR9 rs5743836 (T1237C) polymorphism was performed using real time polymerase chain reaction (RT-PCR). AK155(IL-26) serum levels were determined using ELISA. Results: There is a significantly higher frequency of the mutant homozygous genotype (C/C) and the mutated C allele of TLR9 rs5743836 (T1237C) in COPD patients and in the exacerbated group when compared with the control group and stable COPD patients, respectively, with OR 31.98, 1.8 to 57.7, and OR 3.64, 0.98 to 13.36, respectively. For the mutated C allele, the OR was 3.57, 1.94 to 6.56, p = 0.001, OR 1.83, 1.02 to 3.27, p = 0.041, respectively. In the exacerbated COPD group, there was a significant association between TLR9 rs5743836 SNP and BMI and the lung vital function measures, CRP, and AK155(IL-26). The exacerbated COPD group has higher serum levels of AK155(IL-26) compared with the stable group or when compared with the control group (p = 0.001) for both. AK155(IL-26) serum levels have a positive significant correlation with CRP and BMI and a significant negative correlation with FEV1% and FEV1/FVC in exacerbated COPD patients. Conclusions: Our results demonstrated a relation linking TLR-9 rs5743836 (T1237C) expression and the risk of COPD development and its exacerbation, indicating that dysfunctional polymorphisms of the innate immune genes can affect COPD development and its exacerbation. AK155(IL-26) upregulation was related to decreased lung functionality, systematic inflammatory disease, and COPD exacerbation. Full article
(This article belongs to the Special Issue Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention)
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20 pages, 2411 KB  
Article
Development of PowerMag System II for Isolation of Circulating Tumor Cells with Improved Purity
by Cheng-Rou Ho, Hui-Ju Tsai, Jin-Ru Wang, Chia-Te Wang, Chiuan-Chian Chiou, Ju-Chien Cheng, Sum-Fu Chiang and Ching-Ping Tseng
Biomedicines 2025, 13(2), 431; https://doi.org/10.3390/biomedicines13020431 - 11 Feb 2025
Viewed by 1082
Abstract
Background/Objectives: The PowerMag system (PM) is a platform for the isolation of circulating tumor cells (CTCs) by the depletion of CD45+-leukocytes. However, an EpCAM−CD45− cell population is present in large numbers in the cell filtrates collected by [...] Read more.
Background/Objectives: The PowerMag system (PM) is a platform for the isolation of circulating tumor cells (CTCs) by the depletion of CD45+-leukocytes. However, an EpCAM−CD45− cell population is present in large numbers in the cell filtrates collected by PM. This lowers the purity of the CTCs and negatively impacts their molecular characterization. The aims of this study are to characterize the cellular properties of the EpCAM−CD45− cells and to upgrade the system to improve CTC purity. Methods: A real-time RT-PCR assay, Liu’s stain analysis, and Annexin V (AnxV) binding assay were used to define the cellular properties of the EpCAM−CD45− cells. An upgraded system was developed to remove the EpCAM−CD45− cells and improve the CTC purity. Clinical blood samples were used to evaluate the performance of the system. Results: The EpCAM−CD45− cells were defined as apoptotic cells, which displayed apoptotic body-like morphology and elicited AnxV binding activity. AnxV beads developed in-house can effectively bind and remove EpCAM−CD45− cells from the cell filtrates. An improved generation of a CTCs isolation platform, designated as PM II, was developed by integration of AnxV beads into the workflow to remove the apoptotic cells. PM II recovered CTCs with improved CTC purity by effective removal of the background apoptotic cells. The improved performance of PM II allowed for direct profiling of cancer-related gene mutations by next-generation sequencing without cell picking and further purification. Conclusions: PM II holds great promise as a platform for isolating CTCs with improved purity and for exploring its application in cancer diagnosis and monitoring in a clinical setting. Full article
(This article belongs to the Special Issue Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention)
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Review

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18 pages, 310 KB  
Review
Agnostic Biomarkers and Molecular Signatures in Colorectal Cancer—Guiding Chemotherapy and Predicting Response
by Ilektra Kyrochristou, Georgios D. Lianos, Gerasimia D. Kyrochristou, Georgios Anagnostopoulos, Christina Bali, Stergios Boussios, Michail Mitsis, Dimitrios Schizas and Konstantinos Vlachos
Biomedicines 2025, 13(8), 2038; https://doi.org/10.3390/biomedicines13082038 - 21 Aug 2025
Viewed by 694
Abstract
The concept of agnostic biomarkers—molecular modifications that guide therapy irrespective of tumor origin—has gained increasing relevance in oncology, including colorectal cancer (CRC). This review aims to critically evaluate the role of such biomarkers in CRC, highlighting their clinical significance as therapeutic targets and [...] Read more.
The concept of agnostic biomarkers—molecular modifications that guide therapy irrespective of tumor origin—has gained increasing relevance in oncology, including colorectal cancer (CRC). This review aims to critically evaluate the role of such biomarkers in CRC, highlighting their clinical significance as therapeutic targets and indicators of prognosis. Through a PubMed search using the terms “agnostic treatment AND colorectal cancer,” eight key studies were identified and qualitatively analyzed. We focus on several biomarkers commonly regarded as agnostic across tumor types, including BRAF V600E mutation, receptor tyrosine kinase (RTK) and PI3K fusions, the CpG island methylator phenotype (CIMP), high tumor mutational burden (TMB), and microsatellite instability (MSI). These markers are inspected for their prevalence in CRC, underlying pathophysiological mechanisms of cancer promotion, and predictive or prognostic implications. Moreover, we integrate findings from broader oncologic studies to contextualize the evolving role of agnostic biomarkers beyond organ-specific paradigms. Emerging evidence suggests that leveraging these molecular signatures may inform the use of targeted and immunotherapeutic agents as first-line options in select CRC populations. Collectively, agnostic biomarkers represent an auspicious avenue for personalizing CRC treatment, particularly in advanced-stage disease where traditional treatment options remain limited. Full article
(This article belongs to the Special Issue Advances in Liquid Biopsy from Technological Innovation to Therapeutic Intervention)
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