MicroRNA in Solid Tumor and Hematological Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 40978

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Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
Interests: tumors; cancer research; cell biology; cancer diagnostics; cancer genetics; molecular biology; mouse model
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Dear Colleagues,

MicroRNAs (miRNAs), short non-coding RNA, are involved in physiologic and pathologic processes. They are critically involved in a wide number of processes such as differentiation, development, inflammation, immune response, and cancer. MiRNAs play a key role in cancer pathogenesis by inhibiting gene expression at the post-transcriptional level. Moreover, miRNAs are differentially expressed in tumors compared to normal human tissues and they can be divided into oncomiRNAs and tumor suppressor miRNAs, although some miRNAs can act both roles depending on the cellular context. As a potential therapeutic approach for cancer, extensive studies have demonstrated how to deregulate the small non-coding transcriptome, whether down-regulating the expression of oncogenic miRNAs or overexpressing tumor-suppressive miRNAs. Therefore, the accurate analysis of miRNAs expression from cancer patients might be a useful tool to develop personalized medicine in the future.

This Special Issue will focus on the role of miRNAs in controlling pivotal biological mechanisms that lead to oncogenic transformation and tumor formation, growth, and dissemination, as well as their diagnostic and prognostic significance in different cancer subtypes. Original research manuscripts and comprehensive reviews are both welcome for this call.

Dr. Francesca Lovat
Guest Editor

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Keywords

  • microRNAs
  • solid tumor
  • hematologic malignancies
  • cellular pathway analysis
  • biomarkers
  • cancer genetics
  • gene expression
  • mouse models

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Published Papers (12 papers)

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Editorial

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3 pages, 168 KiB  
Editorial
Editorial to the Special Issue “MicroRNA in Solid Tumor and Hematological Diseases”
by Francesca Lovat
Biomedicines 2021, 9(11), 1678; https://doi.org/10.3390/biomedicines9111678 - 12 Nov 2021
Viewed by 1263
Abstract
In the last two decades, the roles of microRNAs in the biology and progression of human cancer have been extensively studied; at present, these small non-coding RNAs are considered powerful gene regulators [...] Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)

Research

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18 pages, 1911 KiB  
Article
Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study
by Ada Aita, Caterina Millino, Cosimo Sperti, Beniamina Pacchioni, Mario Plebani, Cristiano De Pittà and Daniela Basso
Biomedicines 2021, 9(7), 845; https://doi.org/10.3390/biomedicines9070845 - 20 Jul 2021
Cited by 9 | Viewed by 3867
Abstract
Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures [...] Read more.
Background: Tumor stage predicts pancreatic cancer (PDAC) prognosis, but prolonged and short survivals have been described in patients with early-stage tumors. Circulating microRNA (miRNA) are an emerging class of suitable biomarkers for PDAC prognosis. Our aim was to identify whether serum miRNA signatures predict survival of early-stage PDAC. Methods: Serum RNA from archival 15 stage I-III PDAC patients and 4 controls was used for miRNAs expression profile (Agilent microarrays). PDAC patients with comparable age, gender, diabetes, jaundice and surgery were classified according to survival: less than 14 months (7/15 pts, group A) and more than 22 months (8/15 pts, group B). Bioinformatic data analysis was performed by two-class Significance Analysis of Microarray (SAM) algorithm. Binary logistic regression analyses considering PDAC diagnosis and outcome as dependent variables, and ROC analyses were also performed. Results: 2549 human miRNAs were screened out. At SAM, 76 differentially expressed miRNAs were found among controls and PDAC (FDR = 0.4%), the large majority (50/76, 66%) of them being downregulated in PDAC with respect to controls. Six miRNAs were independently correlated with early PDAC, and among these, hsa-miR-6821-5p was associated with the best ROC curve area in distinguishing controls from early PDAC. Among the 71 miRNAs differentially expressed between groups A and B, the most significant were hsa-miR-3135b expressed in group A only, hsa-miR-6126 and hsa-miR-486-5p expressed in group B only. Eight miRNAs were correlated with the presence of lymph-node metastases; among these, hsa-miR-4669 is of potential interest. hsa-miR-4516, increased in PDAC and found as an independent predictor of survival, has among its putative targets a series of gens involved in key pathways of cancer progression and dissemination, such as Wnt and p53 signalling pathways. Conclusions: A series of serum miRNAs was identified as potentially useful for the early diagnosis of PDAC, and for establishing a prognosis. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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17 pages, 1098 KiB  
Article
Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions
by Igor B. Kovynev, Sergei E. Titov, Pavel S. Ruzankin, Mechti M. Agakishiev, Yuliya A. Veryaskina, Viktor M. Nedel’ko, Tatiana I. Pospelova and Igor F. Zhimulev
Biomedicines 2020, 8(12), 607; https://doi.org/10.3390/biomedicines8120607 - 14 Dec 2020
Cited by 7 | Viewed by 2297
Abstract
Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) [...] Read more.
Introduction: The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA expression profiles in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and hematopoietic conditions induced by non-tumor pathologies (NTP). Methods: A total of 114 cytological samples obtained by sternal puncture and aspiration biopsy of bone marrow (22 ALLs, 44 AMLs, and 48 NTPs) were analyzed by real-time PCR regarding preselected 25 miRNAs. For the classification of the samples, logistic regression was used with balancing of comparison group weights. Results: Our results indicated potential feasibility of (i) differentiating ALL+AML from a nontumor hematopoietic pathology with 93% sensitivity and 92% specificity using miR-150:miR-21, miR-20a:miR-221, and miR-24:nf3 (where nf3 is a normalization factor calculated from threshold cycle values of miR-103a, miR-191, and miR-378); (ii) diagnosing ALL with 81% sensitivity and 81% specificity using miR-181b:miR-100, miR-223:miR-124, and miR-24:nf3; and (iii) diagnosing AML with 81% sensitivity and 84% specificity using miR-150:miR-221, miR-100:miR-24, and miR-181a:miR-191. Conclusion: The results presented herein allow the miRNA expression profile to de used for differentiation between AL and NTP, no matter what AL subtype. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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17 pages, 3771 KiB  
Article
Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex (miR-139-5p and miR-139-3p) in Renal Cell Carcinoma
by Reona Okada, Yusuke Goto, Yasutaka Yamada, Mayuko Kato, Shunichi Asai, Shogo Moriya, Tomohiko Ichikawa and Naohiko Seki
Biomedicines 2020, 8(12), 599; https://doi.org/10.3390/biomedicines8120599 - 12 Dec 2020
Cited by 15 | Viewed by 2624
Abstract
We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p [...] Read more.
We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p < 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p < 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial–mesenchymal transition. Involvement of the miR-139-3p passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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15 pages, 2279 KiB  
Article
Identification of miR-29c-3p as a Robust Normalizer for Urine microRNA Studies in Bladder Cancer
by Julia Oto, Emma Plana, Álvaro Fernández-Pardo, Fernando Cana, Manuel Martínez-Sarmiento, César D. Vera-Donoso, Francisco España and Pilar Medina
Biomedicines 2020, 8(11), 447; https://doi.org/10.3390/biomedicines8110447 - 22 Oct 2020
Cited by 6 | Viewed by 2943
Abstract
Bladder cancer (BC) is among the most frequent malignancies worldwide, being the most expensive cancer to treat and monitor and the most lethal urological cancer. Urine microRNAs (miRNAs) have been proposed as novel non-invasive biomarkers to early diagnose and monitor BC patients in [...] Read more.
Bladder cancer (BC) is among the most frequent malignancies worldwide, being the most expensive cancer to treat and monitor and the most lethal urological cancer. Urine microRNAs (miRNAs) have been proposed as novel non-invasive biomarkers to early diagnose and monitor BC patients in order to avoid the performance of current aggressive diagnostic techniques. However, huge discrepancies arise among studies mainly due to the lack of standardization in the normalization, a crucial step in all miRNA studies. Our aim was to identify the best miRNA normalizer for miRNA studies in urine of BC patients. We evaluated the performance of 110 candidate miRNAs in urine of 35 BC patients and 15 healthy controls by Real Time quantitative Polymerase Chain Reaction (RT-qPCR) followed by a stability analysis with RefFinder. In this screening stage, miR-29c-3p arose as the most stably expressed miRNA in BC and controls, with a good expression level. Stability of miR-29c-3p expression was validated in an independent cohort of 153 BC patients and 57 controls. Finally, we evaluated the robustness of miR-29c-3p as normalizer in the expression study of miR-200c-3p, a potential diagnostic marker for BC. We propose miR-29c-3p as a normalizer for miRNA studies in BC urine. This is the first study that characterizes a reliable normalizer that may allow the comparison of future urine miRNA studies as non-invasive biomarkers for BC diagnosis and monitoring. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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Review

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14 pages, 809 KiB  
Review
MicroRNAs Regulating Hippo-YAP Signaling in Liver Cancer
by Na-Hyun Lee, So Jung Kim and Jeongeun Hyun
Biomedicines 2021, 9(4), 347; https://doi.org/10.3390/biomedicines9040347 - 30 Mar 2021
Cited by 17 | Viewed by 4063
Abstract
Liver cancer is one of the most common cancers worldwide, and its prevalence and mortality rate are increasing due to the lack of biomarkers and effective treatments. The Hippo signaling pathway has long been known to control liver size, and genetic depletion of [...] Read more.
Liver cancer is one of the most common cancers worldwide, and its prevalence and mortality rate are increasing due to the lack of biomarkers and effective treatments. The Hippo signaling pathway has long been known to control liver size, and genetic depletion of Hippo kinases leads to liver cancer in mice through activation of the downstream effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Both YAP and TAZ not only reprogram tumor cells but also alter the tumor microenvironment to exert carcinogenic effects. Therefore, understanding the mechanisms of YAP/TAZ-mediated liver tumorigenesis will help overcome liver cancer. For decades, small noncoding RNAs, microRNAs (miRNAs), have been reported to play critical roles in the pathogenesis of many cancers, including liver cancer. However, the interactions between miRNAs and Hippo-YAP/TAZ signaling in the liver are still largely unknown. Here, we review miRNAs that influence the proliferation, migration and apoptosis of tumor cells by modulating Hippo-YAP/TAZ signaling during hepatic tumorigenesis. Previous findings suggest that these miRNAs are potential biomarkers and therapeutic targets for the diagnosis, prognosis, and treatment of liver cancer. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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19 pages, 681 KiB  
Review
Involvement of microRNA in Solid Cancer: Role and Regulatory Mechanisms
by Ying-Chin Lin, Tso-Hsiao Chen, Yu-Min Huang, Po-Li Wei and Jung-Chun Lin
Biomedicines 2021, 9(4), 343; https://doi.org/10.3390/biomedicines9040343 - 29 Mar 2021
Cited by 14 | Viewed by 3510
Abstract
MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA [...] Read more.
MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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33 pages, 2525 KiB  
Review
The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas
by Pinelopi I. Artemaki, Petros A. Letsos, Ioanna C. Zoupa, Katerina Katsaraki, Paraskevi Karousi, Sotirios G. Papageorgiou, Vasiliki Pappa, Andreas Scorilas and Christos K. Kontos
Biomedicines 2021, 9(4), 333; https://doi.org/10.3390/biomedicines9040333 - 25 Mar 2021
Cited by 19 | Viewed by 5304
Abstract
Normal B-cell development is a tightly regulated complex procedure, the deregulation of which can lead to lymphomagenesis. One common group of blood cancers is the B-cell non-Hodgkin lymphomas (NHLs), which can be categorized according to the proliferation and spread rate of cancer cells [...] Read more.
Normal B-cell development is a tightly regulated complex procedure, the deregulation of which can lead to lymphomagenesis. One common group of blood cancers is the B-cell non-Hodgkin lymphomas (NHLs), which can be categorized according to the proliferation and spread rate of cancer cells into indolent and aggressive ones. The most frequent indolent B-cell NHLs are follicular lymphoma and marginal zone lymphoma. MicroRNAs (miRNAs) are small non-coding RNAs that can greatly influence protein expression. Based on the multiple interactions among miRNAs and their targets, complex networks of gene expression regulation emerge, which normally are essential for proper B-cell development. Multiple miRNAs have been associated with B-cell lymphomas, as the deregulation of these complex networks can lead to such pathological states. The aim of the present review is to summarize the existing information regarding the multifaceted role of miRNAs in indolent B-cell NHLs, affecting the main B-cell subpopulations. We attempt to provide insight into their biological function, the complex miRNA-mRNA interactions, and their biomarker utility in these malignancies. Lastly, we address the limitations that hinder the investigation of the role of miRNAs in these lymphomas and discuss ways that these problems could be overcome in the future. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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20 pages, 1350 KiB  
Review
MiR-7 in Cancer Development
by Petra Korać, Mariastefania Antica and Maja Matulić
Biomedicines 2021, 9(3), 325; https://doi.org/10.3390/biomedicines9030325 - 23 Mar 2021
Cited by 40 | Viewed by 4646
Abstract
MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the [...] Read more.
MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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19 pages, 917 KiB  
Review
MicroRNAs as Predictive Biomarkers of Resistance to Targeted Therapies in Gastrointestinal Tumors
by Valentina Angerilli, Francesca Galuppini, Gianluca Businello, Luca Dal Santo, Edoardo Savarino, Stefano Realdon, Vincenza Guzzardo, Lorenzo Nicolè, Vanni Lazzarin, Sara Lonardi, Fotios Loupakis and Matteo Fassan
Biomedicines 2021, 9(3), 318; https://doi.org/10.3390/biomedicines9030318 - 21 Mar 2021
Cited by 7 | Viewed by 3015
Abstract
The advent of precision therapies against specific gene alterations characterizing different neoplasms is revolutionizing the oncology field, opening novel treatment scenarios. However, the onset of resistance mechanisms put in place by the tumor is increasingly emerging, making the use of these drugs ineffective [...] Read more.
The advent of precision therapies against specific gene alterations characterizing different neoplasms is revolutionizing the oncology field, opening novel treatment scenarios. However, the onset of resistance mechanisms put in place by the tumor is increasingly emerging, making the use of these drugs ineffective over time. Therefore, the search for indicators that can monitor the development of resistance mechanisms and above all ways to overcome it, is increasingly important. In this scenario, microRNAs are ideal candidate biomarkers, being crucial post-transcriptional regulators of gene expression with a well-known role in mediating mechanisms of drug resistance. Moreover, as microRNAs are stable molecules, easily detectable in tissues and biofluids, they are the ideal candidate biomarker to identify patients with primary resistance to a specific targeted therapy and those who have developed acquired resistance. The aim of this review is to summarize the major studies that have investigated the role of microRNAs as mediators of resistance to targeted therapies currently in use in gastro-intestinal neoplasms, namely anti-EGFR, anti-HER2 and anti-VEGF antibodies, small-molecule tyrosine kinase inhibitors and immune checkpoint inhibitors. For every microRNA and microRNA signature analyzed, the putative mechanisms underlying drug resistance were outlined and the potential to be translated in clinical practice was evaluated. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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18 pages, 2947 KiB  
Review
LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression
by Francisca Dias, Cristina Almeida, Ana Luísa Teixeira, Mariana Morais and Rui Medeiros
Biomedicines 2021, 9(2), 195; https://doi.org/10.3390/biomedicines9020195 - 16 Feb 2021
Cited by 6 | Viewed by 3559
Abstract
The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA [...] Read more.
The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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Other

17 pages, 1147 KiB  
Systematic Review
Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision
by Gloria Ravegnini, Pierandrea De Iaco, Francesca Gorini, Giulia Dondi, Isabella Klooster, Eugenia De Crescenzo, Alessandro Bovicelli, Patrizia Hrelia, Anna Myriam Perrone and Sabrina Angelini
Biomedicines 2021, 9(10), 1316; https://doi.org/10.3390/biomedicines9101316 - 26 Sep 2021
Cited by 4 | Viewed by 2337
Abstract
Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification [...] Read more.
Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence. Full article
(This article belongs to the Special Issue MicroRNA in Solid Tumor and Hematological Diseases)
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