Prognostic Value of Circulating IGFBP2 and Related Autoantibodies in Children with Metastatic Rhabdomyosarcomas

Poli, Elena; Zin, Angelica; Cattelan, Manuela; Tombolan, Lucia; Zanetti, Ilaria; Scagnellato, Angela; Bonvini, Paolo; Bisogno, Gianni

doi:10.3390/diagnostics10020115

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…IGFBP2 is a protein-coding gene linked to diseases such as insulin-like growth factor I and malignant ovarian cysts. Its associated pathways include myofascial relaxation and contraction pathway and IGF-1 receptor signaling (46). The elevated expression level of this gene has been shown to accelerate the progression of numerous malignancies and may be used to anticipate the possibility of patient recovery (47).…”

Section: Discussionmentioning

confidence: 99%

m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms

et al. 2022

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BackgroundThe role of epigenetic modulation in immunity is receiving increased recognition—particularly in the context of RNA N6-methyladenosine (m6A) modifications. Nevertheless, it is still uncertain whether m6A methylation plays a role in the onset and progression of intracranial aneurysms (IAs). This study aimed to establish the function of m6A RNA methylation in IA, as well as its correlation with the immunological microenvironment.MethodsOur study included a total of 97 samples (64 IA, 33 normal) in the training set and 60 samples (44 IA, 16 normal) in the validation set to systematically assess the pattern of RNA modifications mediated by 22 m6A regulators. The effects of m6A modifications on immune microenvironment features, i.e., immune response gene sets, human leukocyte antigen (HLA) genes, and infiltrating immune cells were explored. We employed Lasso, machine learning, and logistic regression for the purpose of identifying an m6A regulator gene signature of IA with external data validation. For the unsupervised clustering analysis of m6A modification patterns in IA, consensus clustering methods were employed. Enrichment analysis was used to assess immune response activity along with other functional pathways. The identification of m6A methylation markers was identified based on a protein–protein interaction network and weighted gene co-expression network analysis.ResultsWe identified an m6A regulator signature of IGFBP2, IGFBP1, IGF2BP2, YTHDF3, ALKBH5, RBM15B, LRPPRC, and ELAVL1, which could easily distinguish individuals with IA from healthy individuals. Unsupervised clustering revealed three m6A modification patterns. Gene enrichment analysis illustrated that the tight junction, p53 pathway, and NOTCH signaling pathway varied significantly in m6A modifier patterns. In addition, the three m6A modification patterns showed significant differences in m6A regulator expression, immune microenvironment, and bio-functional pathways. Furthermore, macrophages, activated T cells, and other immune cells were strongly correlated with m6A regulators. Eight m6A indicators were discovered—each with a statistically significant correlation with IA—suggesting their potential as prognostic biological markers.ConclusionOur study demonstrates that m6A RNA methylation and the immunological microenvironment are both intricately correlated with the onset and progression of IA. The novel insight into patterns of m6A modification offers a foundation for the development of innovative treatment approaches for IA.

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Section: Discussionmentioning

confidence: 99%

m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms

et al. 2022

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“…Blocking, washing, probing, development, and quantification procedures were performed as previously described. 29 …”

Section: Methodsmentioning

confidence: 99%

Immunoreactivity against fibroblast growth factor 8 in alveolar rhabdomyosarcoma patients and its involvement in tumor aggressiveness

et al. 2022

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Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma characterized by a very poor prognosis when relapses occur after front-line therapy. Therefore, a major challenge for patients’ management remains the identification of markers associated with refractory and progressive disease. In this context, cancer autoantibodies are natural markers of disease onset and progression, useful to unveil novel therapeutic targets. Herein, we matched autoantibody profiling of alveolar RMS (ARMS) patients with genes under regulatory control of PAX3-FOXO1 transcription factor and revealed fibroblast growth factor 8 (FGF8) as a novel ARMS tumor antigen of diagnostic, prognostic, and therapeutic potential. We demonstrated that high levels of FGF8 autoantibodies distinguished ARMS patients from healthy subjects and represented an independent prognostic factor of better event-free survival. FGF8 was overexpressed in ARMS tumors compared to other types of pediatric soft tissue sarcomas, acting as a positive regulator of cell signaling. Indeed, FGF8 was capable of stimulating ARMS cells migration and expression of pro-angiogenic and metastasis-related factors, throughout MAPK signaling activation. Of note, FGF8 was found to increase in recurrent tumors, independently of PAX3-FOXO1 expression dynamics. Risk of recurrence correlated positively with FGF8 expression levels at diagnosis and reduced FGF8 autoantibodies titer, almost as if to suggest a failure of the immune response to control tumor growth in recurring patients. This study provides evidence about the crucial role of FGF8 in ARMS and the protective function of natural autoantibodies, giving new insights into ARMS biology and laying the foundations for the development of new therapeutic strategies.

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“…However, RMS is rarely located in the larynx [68]. From a histological point of view, RMS can be divided into four subtypes: embryonal (ERMS, accounting for 60-70% of cases), alveolar (ARMS, 20%), pleomorphic, and spindle cells RMS [69]. ERMS is more frequent in children younger than 10 years and is characterized by favorable prognosis.…”

Section: Malignant Laryngeal Tumors Rhabdomyosarcomamentioning

confidence: 99%

Molecular Mechanisms of Carcinogenesis in Pediatric Airways Tumors

Soloperto

Gazzini

Cerullo

2023

IJMS

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Primary tumors of the airways in the pediatric population are very rare entities. For this reason, little is known about the pathogenesis of these neoplasms. Understanding the biology has different practical implications: for example, it could help in the differential diagnosis, have a prognostic significance, or may lead to the development of a targeted therapy. The aim of this article is to present the current knowledge about pediatric airways tumors, focusing on the molecular mechanisms that cause the onset and progression of these neoplasms. After a brief introduction of epidemiology and clinical presentation, the tumorigenesis of the most frequent pediatric airways tumors will be described: Juvenile-onset recurrent respiratory papillomatosis (JORRP), Subglottic Hemangiona (SH), Rhabdomyosarcoma (RMS), and Mucoepidermoid carcinoma (MEC).

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Prognostic Value of Circulating IGFBP2 and Related Autoantibodies in Children with Metastatic Rhabdomyosarcomas

Cited by 9 publications

References 42 publications

m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms

m6A regulator–mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in patients with intracranial aneurysms

Immunoreactivity against fibroblast growth factor 8 in alveolar rhabdomyosarcoma patients and its involvement in tumor aggressiveness

Molecular Mechanisms of Carcinogenesis in Pediatric Airways Tumors

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