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Unveiling the Molecular Landscape Through Next-Generation Liquid Biopsy
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Unveiling the Molecular Landscape Through Next-Generation Liquid Biopsy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 3071

Special Issue Editor

Dr. Valerio Gristina

E-Mail Website
Guest Editor
Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy
Interests: non-small cell lung cancer; small cell lung cancer; liquid biopsy; next-generation technologies

Special Issue Information

Dear Colleagues,

The paradigm shift towards precision oncology, fueled by molecular profiling, has fundamentally reshaped cancer treatment through tailored therapeutic approaches. However, traditional tissue biopsies, the cornerstone of cancer diagnosis, are often hampered by their invasiveness, limited accessibility, and inability to capture tumor heterogeneity. Liquid biopsy, the analysis of tumor-derived materials in biofluids, presents a compelling alternative, addressing these limitations and offering a minimally invasive and dynamic approach to cancer diagnosis and monitoring.

This Special Issue serves as a platform for exploring the cutting-edge frontiers of molecular research in liquid biopsy for precision oncology. We will delve into the diverse spectrum of analytes in liquid biopsies, encompassing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs). Furthermore, we will illuminate the latest advancements in molecular profiling techniques, such as next-generation sequencing (NGS) and digital PCR, enabling the sensitive detection and comprehensive characterization of genomic alterations, gene expression signatures, and epigenetic modifications within these analytes.

The Special Issue encompasses a comprehensive range of sub-topics, including the following:

  • Technological innovations in liquid biopsy analysis: this section will explore novel methodologies and platforms for the sensitive and specific detection and characterization of molecular information from liquid biopsies.
  • Liquid biopsy for early cancer detection and risk stratification: this section will address the potential of liquid biopsy in identifying individuals at high risk of developing cancer and facilitating early detection, paving the way for preventative interventions.
  • Monitoring treatment response and predicting resistance: this section will delve into the role of liquid biopsy in the real-time monitoring of therapeutic response and early detection of resistance mechanisms, allowing for proactive treatment adjustments.
  • Liquid biopsy for personalized treatment selection and targeted therapy development: this section will explore how liquid biopsy can inform personalized treatment decisions and guide the development of novel targeted therapies, maximizing therapeutic efficacy and minimizing adverse effects.
  • Liquid biopsy in clinical trials and personalized medicine implementation: this section will discuss the integration of liquid biopsy into clinical trials and its implications for the successful implementation of personalized medicine in routine clinical practice, ultimately improving patient outcomes.

This Special Issue aspires to provide a comprehensive and insightful overview of the current state-of-the-art and future directions in the molecular research on liquid biopsy for precision oncology.

Dr. Valerio Gristina
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • cfDNA
  • NGS
  • CGP
  • ctDNA, EVs
  • CTCs
  • TEPs
  • methylomics
  • fragmentomics

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Published Papers (2 papers)

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Research

26 pages, 3081 KiB  
Article
Microfluidic Affinity Selection of B-Lineage Cells from Peripheral Blood for Minimal Residual Disease Monitoring in Pediatric B-Type Acute Lymphoblastic Leukemia Patients
by Malgorzata A. Witek, Nicholas E. Larkey, Alena Bartakova, Mateusz L. Hupert, Shalee Mog, Jami K. Cronin, Judy Vun, Keith J. August and Steven A. Soper
Int. J. Mol. Sci. 2024, 25(19), 10619; https://doi.org/10.3390/ijms251910619 - 2 Oct 2024
Viewed by 1254
Abstract
Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report [...] Read more.
Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate the CLCs, perform fluorescence in situ hybridization (FISH), and/or molecular analysis of the CLCs’ mRNA/gDNA. During longitudinal testing of 20 patients throughout induction and consolidation therapy, the MF-MRD performed 116 tests, while only 41 were completed with multiparameter flow cytometry (MFC-MRD) using a bone marrow aspirate, as standard-of-care. Overall, 57% MF-MRD tests were MRD(+) as defined by CLC numbers exceeding a threshold of 5 × 10−4%, which was determined to be the limit of quantitation. Above a threshold of 0.01%, MFC-MRD was positive in 34% of patients. The MF offered the advantage of the opportunity for efficiently processing small volumes of blood (2 mL), which is important in the care of pediatric patients, especially infants. The minimally invasive means of blood collection are of high value when treating patients whose MRD is typically tested using an invasive bone marrow biopsy. MF-MRD detection can be useful for stratification of patients into risk groups and monitoring of patient well-being after completion of treatment for early recognition of potential impending disease recurrence. Full article
(This article belongs to the Special Issue Unveiling the Molecular Landscape Through Next-Generation Liquid Biopsy)
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25 pages, 3566 KiB  
Article
Characterizing the Cell-Free Transcriptome in a Humanized Diffuse Large B-Cell Lymphoma Patient-Derived Tumor Xenograft Model for RNA-Based Liquid Biopsy in a Preclinical Setting
by Philippe Decruyenaere, Willem Daneels, Annelien Morlion, Kimberly Verniers, Jasper Anckaert, Jan Tavernier, Fritz Offner and Jo Vandesompele
Int. J. Mol. Sci. 2024, 25(18), 9982; https://doi.org/10.3390/ijms25189982 - 16 Sep 2024
Viewed by 1087
Abstract
The potential of RNA-based liquid biopsy is increasingly being recognized in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s lymphoma. This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n = [...] Read more.
The potential of RNA-based liquid biopsy is increasingly being recognized in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s lymphoma. This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n = 171) derived from a DLBCL PDTX model, including 27 humanized (HIS) PDTX, 8 HIS non-PDTX, and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform. RNA sequencing data of the formalin-fixed paraffin-embedded (FFPE) tissue and blood plasma samples of the original patient were included. Flow cytometry was performed on immune cells isolated from whole blood, spleen, and bone marrow. Bulk deconvolution was performed using the Tabula Sapiens v1 basis matrix. Both R-CHOP and huCD20-Fc-AFN-CHOP were able to control tumor growth in most mice. Xenograft tumor volume was strongly associated with circulating tumor RNA (ctRNA) concentration (p < 0.001, R = 0.89), as well as with the number of detected human genes (p < 0.001, R = 0.79). Abundance analysis identified tumor-specific biomarkers that were dynamically tracked during tumor growth or treatment. An 8-gene signature demonstrated high accuracy for assessing therapy response (AUC 0.92). The tumoral gene detectability in the ctRNA of the PDTX-derived plasma was associated with RNA abundance levels in the patient’s tumor tissue and blood plasma (p < 0.001), confirming that tumoral gene abundance contributes to the cell-free RNA (cfRNA) profile. Decomposing the transcriptome, however, revealed high inter- and intra-mouse variability, which was lower in the HIS PDTX mice, indicating an impact of human engraftment on the stability and profile of cfRNA. Immunochemotherapy resulted in B cell depletion, and tumor clearance was reflected by a decrease in the fraction of human CD45+ cells. Lastly, bulk deconvolution provided complementary biological insights into the composition of the tumor and circulating immune system. In conclusion, the blood plasma-derived transcriptome serves as a biomarker source in a preclinical PDTX model, enables the assessment of biological pathways, and enhances the understanding of cfRNA dynamics. Full article
(This article belongs to the Special Issue Unveiling the Molecular Landscape Through Next-Generation Liquid Biopsy)
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