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Special Issue "Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 30 April 2023 | Viewed by 7783

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Special Issue Editors

Dr. Marta Dueñas

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Guest Editor

Molecular and Translational Oncology Unit, Department of Biomedical Innovation at CIEMAT, Madrid, Spain
Interests: liquid biopsy and tumor cells biomarkers in genitourinary tumors

Dr. Rodrigo Toledo
E-Mail Website
Guest Editor

Department of Oncology, Gastrointestinal Tumor Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain
Interests: the use of liquid biopsy in cancer research and clinical application

Special Issue Information

Dear Colleagues,

Liquid biopsy has emerged as a reliable tool for tumor surveillance, studying disseminated tumor cells in bone marrow and circulating tumor cells in peripheral blood and providing crucial insights into cancer biology and the metastatic process. More recently, the development of the detection and characterization of circulating tumor DNA (ctDNA) and other molecules either free or as extracellular vessels has finally enabled the arrival of liquid biopsy assays into clinical practice; however, little is known about the circulating tumor microenvironment either at the cellular or biomarker level and its potential implementation to help define the best molecularly targeted therapies for cancer. In this context, this Special Issue will focus on the next frontier for the clinical application of liquid biopsy in cancer treatment, cancer screening, diagnosis, follow-up, and the best personalized therapies as potential future applications. We would like to develop a compendium issue centered in technology, methodologies, and logistics for the eventual integration of liquid biopsy into the clinical workflow.

We are pleased to invite you to participate in this Special Issue that will focus on the state of the art and the latest findings on circulating tumor biomarkers, circulating tumor cells (CTCs), tumor hybrid cells (THCs), as well as ctDNA and ctRNA (coding and noncoding) and protein analysis, and clinical evidence regarding the implementation of liquid biopsy in clinical practice.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Implication of liquid biopsy in cancer diagnosis, prognosis, and clinical management;
More than circulating tumor cells in blood sample characterization;
DNAs, RNAs, and proteins as cancer biomarkers in biofluids;
Liquid biopsy approximations in immunotherapy response prediction.

We look forward to receiving your contributions.

Dr. Marta Dueñas
Dr. Rodrigo Toledo
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. Cancers 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 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
ctRNA
cytokine profiling
tumor biomarkers
CTC
THC

Published Papers (6 papers)

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Research

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Open AccessArticle

Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma

Alicia Garrido-Aranda

Martina Alvarez

Cristina Belendez

Judith Balmaña

and

Ramon Garcia-Escudero

Cancers 2023, 15(6), 1871; https://doi.org/10.3390/cancers15061871 - 21 Mar 2023

Viewed by 513

Abstract

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise to severe toxicities. New methods for early diagnosis are urgently needed to allow for treatment in early disease stages and achieve better clinical outcomes. We conducted a prospective, longitudinal study wherein liquid biopsies from sixteen patients with no clinical diagnoses of OPML and/or OSCC were analyzed for the presence of mutations in cancer genes. The DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evaluation followed over a median time of approximately 2 years. In 9/16 FA patients, we detected mutations in cancer genes (mainly TP53) with minor allele frequencies (MAF) of down to 0.07%. Importantly, all patients that had mutations and clinical follow-up data after mutation detection (n = 6) developed oral precursor lesions or OSCC. The lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations displayed a significantly lower risk of developing precursor lesions or OSCCs. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow for closer surveillance for OSCCs or precursor lesions. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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Open AccessArticle

Plasma-Based microRNA Expression Analysis in Advanced Stage NSCLC Patients Treated with Nivolumab

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Cancers 2022, 14(19), 4739; https://doi.org/10.3390/cancers14194739 - 28 Sep 2022

Cited by 1 | Viewed by 996

Abstract

Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune checkpoint regulation (miR-34a, miR-200b, miR-200c), T-cell activity (miR-155), and the function of myeloid-derived suppressive cells (MDSCs) (miR-223) or regulatory T lymphocytes (Tregs) (miR-146a), in patients with advanced NSCLC (N = 69) treated with anti-PD-1 (Nivolumab) immunotherapy as 2nd or 3rd line of treatment therapy. Plasma levels of circulating miRNAs were analyzed by RT-qPCR before the initiation of immunotherapy. Expression of miR-34a, miR-146a, mir-200c, and miR-223 was found to be associated with response to immunotherapy. High miR-200c expression emerged as an independent prognostic factor for inferior overall survival in all patients with NSCLC (OS, HR: 2.243, 95% CI: 1.208–4.163; p = 0.010) and in patients with non-Squamous (non-SqCC) subtype (N = 38) (HR: 2.809, 95% CI: 1.116–7.074; p = 0.028). Low miR-34a expression independently predicted for shorter OS (HR: 3.189, 95% CI: 1.193–8.527; p = 0.021) in the non-SqCC subgroup. Our findings suggest that alterations in circulating miR-200c and miR-34a expression levels are associated with the response and outcome in patients with advanced NSCLC treated with anti-PD1 immunotherapy. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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Open AccessArticle

A miRNA-Based Prognostic Model to Trace Thyroid Cancer Recurrence

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Cancers 2022, 14(17), 4128; https://doi.org/10.3390/cancers14174128 - 26 Aug 2022

Cited by 3 | Viewed by 1249

Abstract

Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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Figure 1

Open AccessArticle

The Prognostic Value of the Circulating Tumor Cell-Based Four mRNA Scoring System: A New Non-Invasive Setting for the Management of Bladder Cancer

Consuelo Amantini

Federica Maggi

Jacopo Adolfo Rossi de Vermandois

Marilena Gubbiotti

Antonella Giannantoni

and

Maria Beatrice Morelli

Cancers 2022, 14(13), 3118; https://doi.org/10.3390/cancers14133118 - 25 Jun 2022

Viewed by 1219

Abstract

Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells (CTCs) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival (HR = 2.704, 95% CI = 1.010–7.313, Log-rank p < 0.050). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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Review

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Open AccessReview

A Review and In Silico Analysis of Tissue and Exosomal Circular RNAs: Opportunities and Challenges in Thyroid Cancer

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Cancers 2022, 14(19), 4728; https://doi.org/10.3390/cancers14194728 - 28 Sep 2022

Viewed by 1002

Abstract

Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in developing a successful treatment strategy and improving patients’ prognoses. Circular RNAs (circRNAs), a family of non-coding RNAs, have been implicated in several aspects of carcinogenesis in multiple cancers, including TC. In the current review, we aimed to explore the clinical potential of circRNAs as putative diagnostic, prognostic, and therapeutic targets in TC. The current analyses, including genome-wide circRNA screening and functional enrichment for all deregulated circRNA expression signatures, show that circRNAs display atypical contributions, such as sponging for microRNAs, regulating transcription and translation processes, and decoying for proteins. Given their exceptional clinical advantages, such as higher stability, wider abundance, and occurrence in several body fluids, circRNAs are promising prognostic and theranostic biomarkers for TC. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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Open AccessReview

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

Alberto Garrido-Fernández

Clara González-Ojea

Laura Juaneda-Magdalena

Martín E. Lázaro

and

Mónica Martínez-Fernández

Cancers 2022, 14(11), 2626; https://doi.org/10.3390/cancers14112626 - 26 May 2022

Cited by 5 | Viewed by 2083

Abstract

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients. Full article

(This article belongs to the Special Issue Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers)

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