Special Issue "New Advances for the Application of Liquid Biopsies to Manage Cancer Patients"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 30 September 2021.

Special Issue Editor

Dr. Laura Muinelo-Romay
E-Mail Website
Guest Editor
Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Santiago de Compostela 15706, Spain.
Interests: gynecological oncology; endometrial cancer; liquid biopsy; circulating tumor cells; ctDNA

Special Issue Information

Dear Colleagues,

In the last decade, the introduction of precision medicine has revolutionized the oncology field. As part of this new philosophy to fight cancer, liquid biopsies have emerged as a novel tool in medical oncology which has opened new horizons for improving clinical decision making. Tumors release several biomolecules into body fluids that can be used as biomarkers for diagnosis, prognosis, therapy selection, and monitoring. Therefore, although blood is the most widely used type of liquid biopsy, other fluids such as urine, pleural fluid, or saliva can provide valuable information for management of cancer patients. Nowadays, analyses of tissue biopsies still remain the gold standard for diagnosis; however, these analyses have limitations in reflecting tumoral heterogeneity and evolution, which can be improved upon using liquid biopsies.

This Special Issue aims to include original research articles and reviews demonstrating the value of circulating biomarkers for improving cancer management in terms of an early diagnosis, personalized therapy, and dynamic monitoring. To achieve this goal, we will focus on relevant data regarding the clinical interest in circulating tumor cells (CTCs), circulating nucleic acids (ctDNA/ctRNA), and circulating extracellular vesicles (cEVs) in the context of solid tumors.

Dr. Laura Muinelo-Romay
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 papers will be 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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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 2200 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
  • circulating tumor cells (CTCs)
  • circulating tumor DNA (ctDNA)
  • circulating tumor RNA (ctRNA)
  • circulating extracellular vesicles (cEVs)
  • cancer diagnosis
  • therapy selection/monitoring

Published Papers (5 papers)

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Research

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Article
High-Throughput Proteomic Profiling of Nipple Aspirate Fluid from Breast Cancer Patients Compared with Non-Cancer Controls: A Step Closer to Clinical Feasibility
J. Clin. Med. 2021, 10(11), 2243; https://doi.org/10.3390/jcm10112243 - 21 May 2021
Viewed by 497
Abstract
Background: Early detection of breast cancer (BC) is critical for increasing survival rates. However, current imaging approaches can provide ambiguous results, requiring invasive tissue biopsy for a definitive diagnosis. Multi-dimensional mass spectrometric analysis has highlighted the invaluable potential of nipple aspirate fluid (NAF) [...] Read more.
Background: Early detection of breast cancer (BC) is critical for increasing survival rates. However, current imaging approaches can provide ambiguous results, requiring invasive tissue biopsy for a definitive diagnosis. Multi-dimensional mass spectrometric analysis has highlighted the invaluable potential of nipple aspirate fluid (NAF) as a non-invasive source of early detection biomarkers, by identifying a multitude of proteins representative of the changing breast microenvironment. However, technical challenges with biomarker validation in large cohorts remain due to low sample throughput, impeding progress towards clinical utility. Rather, by employing a high-throughput method, that is more practicable for clinical utility, perturbations of the most abundant NAF proteins in BC patients compared with non-cancer (NC) controls could be monitored and validated in larger groups. Method: We characterized matched NAF pairs from BC (n = 9) and NC (n = 4) volunteers, using a rapid one dimensional liquid chromatography-mass spectrometry (1D LC-MS/MS) approach. Results: Overall, 198 proteins were relatively quantified, of which 40 were significantly differentiated in BC samples, compared with NC (p ≤ 0.05), with 26 upregulated and 14 downregulated. An imbalance in immune response and proteins regulating cell growth, maintenance and communication were identified. Conclusions: Our findings show 1D LC-MS/MS can quantify changes reflected in the NAF proteome associated with breast cancer development. Full article
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Article
Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant Cases
J. Clin. Med. 2021, 10(1), 87; https://doi.org/10.3390/jcm10010087 - 29 Dec 2020
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Abstract
Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were [...] Read more.
Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance. RESULTS: Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases. Conclusions: PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management. Full article
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Article
Global Gene Expression Characterization of Circulating Tumor Cells in Metastasic Castration-Resistant Prostate Cancer Patients
J. Clin. Med. 2020, 9(7), 2066; https://doi.org/10.3390/jcm9072066 - 01 Jul 2020
Cited by 2 | Viewed by 796
Abstract
Background: Current therapeutic options in the course of metastatic castration-resistant prostate cancers (mCRPC) reinforce the need for reliable tools to characterize the tumor in a dynamic way. Circulating tumor cells (CTCs) have emerged as a viable solution to the problem, whereby patients with [...] Read more.
Background: Current therapeutic options in the course of metastatic castration-resistant prostate cancers (mCRPC) reinforce the need for reliable tools to characterize the tumor in a dynamic way. Circulating tumor cells (CTCs) have emerged as a viable solution to the problem, whereby patients with a variety of solid tumors, including PC, often do not have recent tumor tissue available for analysis. The biomarker characterization in CTCs could provide insights into the current state of the disease and an overall picture of the intra-tumor heterogeneity. Methods: in the present study, we applied a global gene expression characterization of the CTC population from mCRPC (n = 9), with the goal to better understand the biology of these cells and identify the relevant molecules favoring this tumor progression. Results: This analysis allowed the identification of 50 genes specifically expressed in CTCs from patients. Six of these markers (HOXB13, QKI, MAOA, MOSPD1, SDK1, and FGD4), were validated in a cohort of 28 mCRPC, showing clinical interest for the management of these patients. Of note, the activity of this CTC signature was related to the regulation of MYC, a gene strongly implicated in the biology of mCRPC. Conclusions: Overall, our results represent new evidence on the great value of CTCs as a non-invasive biopsy to characterize PC. Full article
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Article
Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study
J. Clin. Med. 2020, 9(6), 1738; https://doi.org/10.3390/jcm9061738 - 04 Jun 2020
Cited by 2 | Viewed by 1005
Abstract
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. [...] Read more.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. In this pilot study, we explored the feasibility of circulating tumor (ct) DNA analysis to select patients for CRS-HIPEC. Thirty patients eligible for CRS-HIPEC provided blood samples preoperatively and during follow-up if the procedure was completed. Targeted Next-Generation Sequencing (NGS) of DNA from PMs was used to identify bespoke mutations that were subsequently tested in corresponding plasma cell-free (cf) DNA samples using droplet digital (dd) PCR. CtDNA was detected preoperatively in cfDNA samples from 33% of patients and was associated with a reduced disease-free survival (DFS) after CRS-HIPEC (median 6.0 months vs median not reached, p = 0.016). This association could indicate the presence of undiagnosed systemic metastases or an increased metastatic potential of the tumors. We demonstrate the feasibility of ctDNA to serve as a preoperative marker of recurrence in patients with PMs of colorectal cancer using a highly sensitive technique. A more appropriate treatment for patients with preoperative ctDNA detection may be systemic chemotherapy in addition to, or instead of, CRS-HIPEC. Full article
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Review

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Review
Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management
J. Clin. Med. 2020, 9(9), 2749; https://doi.org/10.3390/jcm9092749 - 25 Aug 2020
Cited by 11 | Viewed by 946
Abstract
One in every four deaths is due to cancer in Europe. In view of its increasing incidence, cancer became the leading cause of death and disease burden in Denmark, France, the Netherlands, and the UK. Without essential improvements in cancer prevention, an additional [...] Read more.
One in every four deaths is due to cancer in Europe. In view of its increasing incidence, cancer became the leading cause of death and disease burden in Denmark, France, the Netherlands, and the UK. Without essential improvements in cancer prevention, an additional 775,000 cases of annual incidence have been prognosed until 2040. Between 1995 and 2018, the direct costs of cancer doubled from EUR 52 billion to EUR 103 billion in Europe, and per capita health spending on cancer increased by 86% from EUR 105 to EUR 195 in general, whereby Austria, Germany, Switzerland, Benelux, and France spend the most on cancer care compared to other European countries. In view of the consequent severe socio-economic burden on society, the paradigm change from a reactive to a predictive, preventive, and personalized medical approach in the overall cancer management is essential. Concepts of predictive, preventive, and personalized medicine (3PM) demonstrate a great potential to revise the above presented trends and to implement cost-effective healthcare that benefits the patient and society as a whole. At any stage, application of early and predictive diagnostics, targeted prevention, and personalization of medical services are basic pillars making 3PM particularly attractive for the patients as well as ethical and cost-effective healthcare. Optimal 3PM approach requires novel instruments such as well-designed liquid biopsy application. This review article highlights current achievements and details liquid biopsy approaches specifically in cancer management. 3PM-relevant expert recommendations are provided. Full article
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