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Diagnostics
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Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer
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Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 19524

Special Issue Editors

Prof. Dr. Ewa Bien

E-Mail Website
Guest Editor
Department of Pediatric Hematology & Oncology, Medical University of Gdansk, Gdansk, Poland
Interests: pediatrics; oncology; hematology
Prof. Dr. Janina Baranowska-Kortylewicz

E-Mail Website
Guest Editor
College of Pharmacy, Department of Pharmaceutical Sciences University of Nebraska Medical Center, 986125 Nebraska Medical Center, Omaha, NE 68198-6125, USA
Interests: neuroblastoma biomarkers; novel theranostics

Special Issue Information

Dear Colleagues,

This Special Issue on diagnostic, prognostic and predictive markers in pediatric cancer aims to present the current achievements and future directions of scientific investigations in terms of searching for novel diagnostic, prognostic and predictive markers in malignant solid tumors occurring in children and adolescents. The topic is of particular importance because pediatric cancers are a diverse group of neoplasms of different origins with various biological courses and prognoses, and most of them lack reliable markers used routinely in clinical practice. Fast development and application of the genetic, molecular, immunohistochemical, immunological and biochemical methods have enabled the identification of new promising markers that might help to diagnose selected malignant solid tumors developing in childhood and adolescence. This Special Issue aims to present the most important recent achievements in this unique field of oncology.

Prof. Dr. Ewa Bien
Prof. Dr. Janina Baranowska-Kortylewicz
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. Diagnostics 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

  • Malignant solid tumors
  • Soft tissue sarcomas
  • Central nervous system tumors
  • Melanoma
  • Very rare tumors
  • Children and adolescents

Published Papers (5 papers)

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Research

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22 pages, 1155 KiB  
Article
Polish Multi-Institutional Study of Children with Ependymoma—Clinical Practice Outcomes in the Light of Prospective Trials
by Aleksandra Napieralska, Agnieszka Mizia-Malarz, Weronika Stolpa, Ewa Pawłowska, Małgorzata A. Krawczyk, Katarzyna Konat-Bąska, Aneta Kaczorowska, Arkadiusz Brąszewski and Maciej Harat
Diagnostics 2021, 11(12), 2360; https://doi.org/10.3390/diagnostics11122360 - 14 Dec 2021
Viewed by 2070
Abstract
We performed a multi-institutional analysis of 74 children with ependymoma to evaluate to what extent the clinical outcome of prospective trials could be reproduced in routine practice. The evaluation of factors that correlated with outcome was performed with a log rank test and [...] Read more.
We performed a multi-institutional analysis of 74 children with ependymoma to evaluate to what extent the clinical outcome of prospective trials could be reproduced in routine practice. The evaluation of factors that correlated with outcome was performed with a log rank test and a Cox proportional-hazard model. Survival was estimated with the Kaplan–Meier method. The majority of patients had brain tumours (89%). All had surgery as primary treatment, with adjuvant radiotherapy (RTH) and chemotherapy (CTH) applied in 78% and 57%, respectively. Median follow-up was 80 months and 18 patients died. Five- and 10-year overall survival (OS) was 83% and 73%. Progression was observed in 32 patients, with local recurrence in 28 cases. The presence of metastases was a negative prognostic factor for OS. Five- and 10-year progression-free survival (PFS) was 55% and 40%, respectively. The best outcome in patients with non-disseminated brain tumours was observed when surgery was followed by RTH (+/−CTH afterwards; p = 0.0001). Children under 3 years old who received RTH in primary therapy had better PFS (p = 0.010). The best outcome of children with ependymoma is observed in patients who received radical surgery followed by RTH, and irradiation should not be omitted in younger patients. The role of CTH remains debatable. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer)
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16 pages, 7963 KiB  
Article
High Expression of Solute Carrier Family 2 Member 1 (SLC2A1) in Cancer Cells Is an Independent Unfavorable Prognostic Factor in Pediatric Malignant Peripheral Nerve Sheath Tumor
by Malgorzata A. Krawczyk, Michal Kunc, Malgorzata Styczewska, Anna Gabrych, Gabrielle Karpinsky, Ewa Izycka-Swieszewska and Ewa Bien
Diagnostics 2021, 11(4), 598; https://doi.org/10.3390/diagnostics11040598 - 26 Mar 2021
Cited by 6 | Viewed by 2051
Abstract
Malignant peripheral nerve sheath tumor (MPNST) in children is a rare mesenchymal malignancy developing predominantly in the setting of neurofibromatosis type 1. The prognosis in advanced MPNST is poor therefore new prognostic markers are highly needed for optimal therapeutic decisions. In many solid [...] Read more.
Malignant peripheral nerve sheath tumor (MPNST) in children is a rare mesenchymal malignancy developing predominantly in the setting of neurofibromatosis type 1. The prognosis in advanced MPNST is poor therefore new prognostic markers are highly needed for optimal therapeutic decisions. In many solid tumors, the bidirectional interactions between hypoxia and inflammation in the tumor microenvironment via functions of tumor-associated cells, like neutrophils, lymphocytes and macrophages, have been investigated recently. There is no data whether in MPNST hypoxic microenvironment may translate into systemic inflammation, which is a well-established factor for worse prognosis in cancer patients. Therefore, we investigated the prognostic significance of markers of tumor hypoxia and systemic inflammation in 26 pediatric malignant peripheral nerve sheath tumors (MPNST). Tumor tissue microarrays were stained for hypoxia-inducible factor-1α (HIF1A), solute carrier family 2 member 1 (SLC2A1, also known as glucose transporter 1 (GLUT1)), carbonic anhydrase 9 (CA9), and vascular endothelial growth factor A (VEGFA) and classified into low- or high-expression groups. Baseline complete blood counts and C-reactive protein (CRP) levels were collected for all cases. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated from age-adjusted complete blood count parameters. Both 10-year RFS and OS were significantly lower in patients with high NLR values (17% vs. 75%, p = 0.009, q = 0.018; and 31% vs. 100%, p = 0.0077, q = 0.014; respectively). Ten-year-OS was significantly lower in patients with high expression of SLC2A1 (20.00% vs. 94%, p < 0.001, log-rank), high expression of HIF1A (23% vs. 79%, p = 0.016, log-rank), and CRP higher than 31 mg/L (11% vs. 82%, p = 0.003, q = 0.009). Cox’s proportional hazard regression analysis revealed that high expression of SLC2A1 (HR = 3.31, 95% CI = 1.08–10.09, p = 0.036) and VEGFA (HR = 4.40, 95% CI = 0.95–20.34, p = 0.058) were the independent factors predicting relapse, whereas high SLC2A1 was identified as the independent risk factor for death (HR = 12.20, 95% CI = 2.55–58.33, p = 0.002). Patients with high expression of hypoxic markers and low or high NLR/CRP values had the highest events rate, patients with low hypoxic markers and high NLR/CRP had intermediate events rate, while patients with low hypoxic markers and low NLR/CRP had the lowest events rate. SLC2A1 and VEGFA are promising novel prognostic factors in pediatric MPNST. Correlations between hypoxic and systemic inflammatory markers suggest the interplay between local tumor hypoxia and systemic inflammation. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer)
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Review

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18 pages, 3166 KiB  
Review
Cell Signaling Pathways That Promote Radioresistance of Cancer Cells
by Michel M. Ouellette, Sumin Zhou and Ying Yan
Diagnostics 2022, 12(3), 656; https://doi.org/10.3390/diagnostics12030656 - 08 Mar 2022
Cited by 28 | Viewed by 4396
Abstract
Radiation therapy (RT) is a standard treatment for solid tumors and about 50% of patients with cancer, including pediatric cancer, receive RT. While RT has significantly improved the overall survival and quality of life of cancer patients, its efficacy has still been markedly [...] Read more.
Radiation therapy (RT) is a standard treatment for solid tumors and about 50% of patients with cancer, including pediatric cancer, receive RT. While RT has significantly improved the overall survival and quality of life of cancer patients, its efficacy has still been markedly limited by radioresistance in a significant number of cancer patients (intrinsic or acquired), resulting in failure of the RT control of the disease. Radiation eradicates cancer cells mainly by causing DNA damage. However, radiation also concomitantly activates multiple prosurvival signaling pathways, which include those mediated by ATM, ATR, AKT, ERK, and NF-κB that promote DNA damage checkpoint activation/DNA repair, autophagy induction, and/or inhibition of apoptosis. Furthermore, emerging data support the role of YAP signaling in promoting the intrinsic radioresistance of cancer cells, which occurs through its activation of the transcription of many essential genes that support cell survival, DNA repair, proliferation, and the stemness of cancer stem cells. Together, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance. Thus, targeting these prosurvival signaling pathways could potentially improve the radiosensitivity of cancer cells. In this review, we summarize the contribution of these pathways to the radioresistance of cancer cells. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer)
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16 pages, 285 KiB  
Review
Diagnostic, Prognostic and Predictive Markers in Pediatric Germ Cell Tumors—Past, Present and Future
by Michalina Jezierska, Ada Gawrychowska and Joanna Stefanowicz
Diagnostics 2022, 12(2), 278; https://doi.org/10.3390/diagnostics12020278 - 21 Jan 2022
Cited by 6 | Viewed by 3658
Abstract
Germ cell tumors (GCTs) are a heterogenous group of neoplasms in children and young adults, in which serum tumor markers have been demonstrated to be highly sensitive diagnostic and monitoring tools. The known "old" serum biomarkers, alpha-fetoprotein (AFP), human choriogonadotropin (β-hCG) and lactate [...] Read more.
Germ cell tumors (GCTs) are a heterogenous group of neoplasms in children and young adults, in which serum tumor markers have been demonstrated to be highly sensitive diagnostic and monitoring tools. The known "old" serum biomarkers, alpha-fetoprotein (AFP), human choriogonadotropin (β-hCG) and lactate dehydrogenase (LDH), have some limitations in sensitivity and specificity. MIRNAs from the miR-371~373 (chromosomal locus 19q13.41) and miR-302/367 (4q25) clusters are universally over-expressed in malignant GCT tissue samples. The levels of miRNAs from these clusters are elevated in the serum. They seem to be highly sensitive and specific in malignant GCTs diagnosis and disease assessment during treatment and follow-up. The aim of our review was to present the role of serum tumor markers in the clinical staging, treatment monitoring and follow-up of pediatric patients with GCTs and show new possibilities. The serum levels of miRNAs seem to be a new, promising essential tool in the clinical management of GCTs. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer)
25 pages, 2492 KiB  
Review
Subgroup-Specific Diagnostic, Prognostic, and Predictive Markers Influencing Pediatric Medulloblastoma Treatment
by Sutapa Ray, Nagendra K. Chaturvedi, Kishor K. Bhakat, Angie Rizzino and Sidharth Mahapatra
Diagnostics 2022, 12(1), 61; https://doi.org/10.3390/diagnostics12010061 - 28 Dec 2021
Cited by 12 | Viewed by 6089
Abstract
Medulloblastoma (MB) is the most common malignant central nervous system tumor in pediatric patients. Mainstay of therapy remains surgical resection followed by craniospinal radiation and chemotherapy, although limitations to this therapy are applied in the youngest patients. Clinically, tumors are divided into average [...] Read more.
Medulloblastoma (MB) is the most common malignant central nervous system tumor in pediatric patients. Mainstay of therapy remains surgical resection followed by craniospinal radiation and chemotherapy, although limitations to this therapy are applied in the youngest patients. Clinically, tumors are divided into average and high-risk status on the basis of age, metastasis at diagnosis, and extent of surgical resection. However, technological advances in high-throughput screening have facilitated the analysis of large transcriptomic datasets that have been used to generate the current classification system, dividing patients into four primary subgroups, i.e., WNT (wingless), SHH (sonic hedgehog), and the non-SHH/WNT subgroups 3 and 4. Each subgroup can further be subdivided on the basis of a combination of cytogenetic and epigenetic events, some in distinct signaling pathways, that activate specific phenotypes impacting patient prognosis. Here, we delve deeper into the genetic basis for each subgroup by reviewing the extent of cytogenetic events in key genes that trigger neoplastic transformation or that exhibit oncogenic properties. Each of these discussions is further centered on how these genetic aberrations can be exploited to generate novel targeted therapeutics for each subgroup along with a discussion on challenges that are currently faced in generating said therapies. Our future hope is that through better understanding of subgroup-specific cytogenetic events, the field may improve diagnosis, prognosis, and treatment to improve overall quality of life for these patients. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Markers in Pediatric Cancer)
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