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Open AccessEditorial

Circulating miRNAs as Tumor Biomarkers: A Preface to the Special Issue

by Athina N. Markou

Cancers 2020, 12(12), 3836; https://doi.org/10.3390/cancers12123836 - 18 Dec 2020

Cited by 2 | Viewed by 1401

Abstract

Nowadays, therapeutic strategies in cancer are subsequently defined according to the molecular profile of the tissue [...] Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

Research

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15 pages, 2156 KiB

Open AccessFeature PaperArticle

Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

by Sara Reis Moura, Hugo Abreu, Carla Cunha, Cláudia Ribeiro-Machado, Carla Oliveira, Mario Adolfo Barbosa, Herlander Marques and Maria Inês Almeida

Cancers 2021, 13(21), 5258; https://doi.org/10.3390/cancers13215258 - 20 Oct 2021

Cited by 5 | Viewed by 3191

Abstract

Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miRNAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel [...] Read more.

Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miRNAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel of miRNAs associated with MM onset and progression, or with bone remodeling, was analyzed in the plasma of 82 subjects (47 MM patients; 35 healthy controls). Results show that miR-16-5p, miR-20a-5p, and miR-21-5p are differently expressed between MM patients and healthy controls. Receiver operating characteristic analyses indicate that their combined expression has potential as a molecular marker (Area Under the Curve, AUC of 0.8249). Furthermore, significant correlations were found between the analyzed miRNAs and disease stage, treatment, β2 microglobulin, serum albumin and creatinine levels, but not with calcium levels or genetic alterations. In this cohort, 65.96% of MM patients had bone lesions, the majority of which were in the vertebrae. Additionally, miR-29c-3p was decreased in patients with osteolytic lesions compared with patients without bone disease. Interestingly, circulating levels of miR-29b-3p correlated with cervical and thoracic vertebral lesions, while miR-195-5p correlated with thoracic lesions. Our findings suggest circulating miRNAs can be promising biomarkers for MM diagnosis and that their levels correlate with myeloma bone disease and osteolytic lesions. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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11 pages, 1381 KiB

Open AccessArticle

Sampling, Logistics, and Analytics of Urine for RT-qPCR-based Diagnostics

by Rosel Kretschmer-Kazemi Far, Kirsten Frank and Georg Sczakiel

Cancers 2021, 13(17), 4381; https://doi.org/10.3390/cancers13174381 - 30 Aug 2021

Cited by 3 | Viewed by 2069

Abstract

Body fluids in the context of cancer diagnosis are the primary source of liquid biopsy, i.e., biomarker detection that includes blood and serum, urine, and saliva. RNA represents a particular class of biomarkers because it is thought to monitor the current status of [...] Read more.

Body fluids in the context of cancer diagnosis are the primary source of liquid biopsy, i.e., biomarker detection that includes blood and serum, urine, and saliva. RNA represents a particular class of biomarkers because it is thought to monitor the current status of gene expression in humans, in organs, and if present, also in tumors. In case of bladder cancer, we developed a scheme that describes, in detail, all steps from the collection of urine samples from patients, stabilization of samples, their transportation, storage, and marker analysis by qPCR-based technology. We find that urine samples prepared according to this protocol show stability of RNA over more than 10 days at unchilled temperatures during shipping. A specific procedure of primer design and amplicon evaluation allows a specific assignment of PCR products to human genomics and transcriptomics data collections. In summary, we describe a technical option for the robust acquisition of urine samples and the quantitative detection of RNA-based tumor markers in case of bladder cancer patients. This protocol is for general use, and we describe that it works for any RNA-based tumor marker in urine of cancer patients. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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17 pages, 2003 KiB

Open AccessArticle

A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

by Aristea-Maria Papanota, Panagiotis Tsiakanikas, Christos K. Kontos, Panagiotis Malandrakis, Christine-Ivy Liacos, Ioannis Ntanasis-Stathopoulos, Nikolaos Kanellias, Maria Gavriatopoulou, Efstathios Kastritis, Margaritis Avgeris, Meletios-Athanasios Dimopoulos, Andreas Scorilas and Evangelos Terpos

Cancers 2021, 13(15), 3877; https://doi.org/10.3390/cancers13153877 - 31 Jul 2021

Cited by 12 | Viewed by 2435

Abstract

Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated [...] Read more.

Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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13 pages, 1144 KiB

Open AccessArticle

PlasmiR: A Manual Collection of Circulating microRNAs of Prognostic and Diagnostic Value

by Spyros Tastsoglou, Marios Miliotis, Ioannis Kavakiotis, Athanasios Alexiou, Eleni C. Gkotsi, Anastasia Lambropoulou, Vasileios Lygnos, Vasiliki Kotsira, Vasileios Maroulis, Dimitrios Zisis, Giorgos Skoufos and Artemis G. Hatzigeorgiou

Cancers 2021, 13(15), 3680; https://doi.org/10.3390/cancers13153680 - 22 Jul 2021

Cited by 9 | Viewed by 3148

Abstract

Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene [...] Read more.

Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR’s entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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14 pages, 3209 KiB

Open AccessArticle

Identification of a Two-MicroRNA Signature in Plasma as a Novel Biomarker for Very Early Diagnosis of Breast Cancer

by Anna Adam-Artigues, Iris Garrido-Cano, Juan Antonio Carbonell-Asins, Ana Lameirinhas, Soraya Simón, Belén Ortega-Morillo, María Teresa Martínez, Cristina Hernando, Vera Constâncio, Octavio Burgues, Begoña Bermejo, Rui Henrique, Ana Lluch, Carmen Jerónimo, Pilar Eroles and Juan Miguel Cejalvo

Cancers 2021, 13(11), 2848; https://doi.org/10.3390/cancers13112848 - 7 Jun 2021

Cited by 17 | Viewed by 3237

Abstract

The early diagnosis of breast cancer is essential to improve patients’ survival rate. In this context, microRNAs have been described as potential diagnostic biomarkers for breast cancer. Particularly, circulating microRNAs have a strong value as non-invasive biomarkers. Herein, we assessed the potential of [...] Read more.

The early diagnosis of breast cancer is essential to improve patients’ survival rate. In this context, microRNAs have been described as potential diagnostic biomarkers for breast cancer. Particularly, circulating microRNAs have a strong value as non-invasive biomarkers. Herein, we assessed the potential of a microRNA signature based on miR-30b-5p and miR-99a-5p levels in plasma as a diagnostic biomarker for breast cancer. This two-microRNA signature was constructed by Principal Component Analysis and its prognostic value was assessed in a discovery cohort and blindly validated in a second cohort from an independent institution. ROC curve analysis and biomarker performance parameter evaluation demonstrated that our proposed signature presents a high value as a non-invasive biomarker for very early detection of breast cancer. In addition, pathway enrichment analysis identified three of the well-known pathways involved in cancer as targets of the two microRNAs. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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13 pages, 1116 KiB

Open AccessArticle

MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

by Irena Abramovic, Borna Vrhovec, Lucija Skara, Alen Vrtaric, Nora Nikolac Gabaj, Tomislav Kulis, Goran Stimac, Dejan Ljiljak, Boris Ruzic, Zeljko Kastelan, Bozo Kruslin, Floriana Bulic-Jakus, Monika Ulamec, Ana Katusic-Bojanac and Nino Sincic

Cancers 2021, 13(9), 2068; https://doi.org/10.3390/cancers13092068 - 25 Apr 2021

Cited by 22 | Viewed by 2990

Abstract

Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression [...] Read more.

Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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Review

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21 pages, 1292 KiB

Open AccessReview

Circulating MicroRNAs in Gastrointestinal Cancer

by Masahisa Ohtsuka, Kazuya Iwamoto, Atsushi Naito, Mitsunobu Imasato, Satoshi Hyuga, Yujiro Nakahara, Manabu Mikamori, Kenta Furukawa, Jeongho Moon, Tadafumi Asaoka, Kentaro Kishi, Awad Shamma, Hiroki Akamatsu, Tsunekazu Mizushima and Hirofumi Yamamoto

Cancers 2021, 13(13), 3348; https://doi.org/10.3390/cancers13133348 - 3 Jul 2021

Cited by 11 | Viewed by 2947

Abstract

Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but [...] Read more.

Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers. Full article

(This article belongs to the Special Issue Circulating miRNAs as Tumor Biomarkers)

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