Protein Tyrosine Phosphatases in Neuroblastoma: Emerging Roles as Biomarkers and Therapeutic Targets

Nunes‐Xavier, Caroline E.; Zaldumbide, Laura; Mosteiro, Lorena; Almaraz, Ricardo López; Andoin, Nagore García de; Aguirre, Pablo; Emaldi, Maite; Torices, Leire; López, José I.; Pulido, Rafael

doi:10.3389/fcell.2021.811297

Cited by 4 publications

(6 citation statements)

References 205 publications

(220 reference statements)

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“…Recent studies have shown numerous molecular biomarkers in cancer (35)(36)(37). For example, KNG1 and FGG have been found to be correlated with the progression and prognosis of hepatocellular carcinoma (38,39), and SPP1 and CAV1 with overall survival in lung adenocarcinoma (40,41).…”

Section: Discussionmentioning

confidence: 99%

Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis

Lin¹,

Zeng²,

Liang³

et al. 2022

J Gastrointest Oncol

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Background: Colorectal cancer (CRC) is a common global malignancy associated with high invasiveness, high metastasis, and poor prognosis. CRC commonly metastasizes to the liver, where the treatment of metastasis is both difficult and an important topic in current CRC management.Methods: Microarrays data of human CRC with liver metastasis (CRCLM) were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database to identify potential key genes. Differentially expressed (DE) genes (DEGs) and DEmiRNAs of primary CRC tumor tissues and metastatic liver tissues were identified. Microenvironment Cell Populations (MCP)-counter was used to estimate the abundance of immune cells in the tumor micro-environment (TME), and weighted gene correlation network analysis (WGCNA) was used to construct the co-expression network analysis.Gene Ontology and Kyoto Encyclopaedia of Gene and Genome (KEGG) pathway enrichment analyses were conducted, and the protein-protein interaction (PPI) network for the DEGs were constructed and gene modules were screened.Results: Thirty-five pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened, and 610 DEGs (265 up-regulated and 345 down-regulated) and 284 DEmiRNAs were identified. The DEGs were mainly enriched in the complement and coagulation cascade pathways and renin secretion. Immune infiltrating cells including neutrophils, monocytic lineage, and cancer-associated fibroblasts (CAFs) differed significantly between primary tumor tissues and metastatic liver tissues. WGCN analysis obtained 12 modules and identified 62 genes with significant interactions which were mainly related to complement and coagulation cascade and the focal adhesion pathway. The best subset regression analysis and backward stepwise regression analysis were performed, and eight genes were determined, including F10, FGG, KNG1, MBL2, PROC, SERPINA1, CAV1, and SPP1. Further analysis showed four genes, including FGG, KNG1, CAV1, and SPP1 were significantly associated with CRCLM.Conclusions: Our study implies complement and coagulation cascade and the focal adhesion pathway play a significant role in the development and progression of CRCLM, and FGG, KNG1, CAV1, and SPP1 may be metastatic markers for its early diagnosis.

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Section: Discussionmentioning

confidence: 99%

Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis

Lin¹,

Zeng²,

Liang³

et al. 2022

J Gastrointest Oncol

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“…Moreover, PTPRD has been involved in regulating neuronal survival and differentiation during brain development via its effects upon cell growth and differentiation by directly dephosphorylating specific protein substrates on tyrosine residues [15]. Thus, PTPRD may act as an intracellular transducer during neu-ronal development, responding to external stimuli that drive cell proliferation, survival, and differentiation [16]. Furthermore, PTPRD appears to be involved in the regulation of cognitive functions, such as learning and memory, since PTPRD-deficient mice have impaired cognitive functions, including deficits in contextual fear memory and spatial learning [17].…”

Section: Introductionmentioning

confidence: 99%

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma

Orton,

Karkia,

Mustafov

et al. 2024

Cancers

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Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.

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“…Therefore, despite successfully identifying many prognostic genes, these studies heavily ignored tumor heterogeneity. NB is a type of tumor intimately related to the early development and differentiation of neuroendocrine (NE) cells ( Nunes-Xavier et al, 2021 ). The intrinsic and extrinsic features of malignant NE cells can be precisely characterized using single-cell RNA sequencing (scRNA-seq) technology, which enables gene profiling and discovery of oncogenic cellular populations and associated marker genes at single-cell resolution ( Tang et al, 2009 ; Patel et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma

Yan

Liu

Cao

et al. 2022

Front. Neuroinform.

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BackgroundNeuroblastoma is the most common extracranial solid tumor of childhood, arising from the sympathetic nervous system. High-risk neuroblastoma (HRNB) remains a major therapeutic challenge with low survival rates despite the intensification of therapy. This study aimed to develop a malignant-cell marker gene signature (MMGS) that might serve as a prognostic indicator in HRNB patients.MethodsMulti-omics datasets, including mRNA expression (single-cell and bulk), DNA methylation, and clinical information of HRNB patients, were used to identify prognostic malignant cell marker genes. MMGS was established by univariate Cox analysis, LASSO, and stepwise multivariable Cox regression analysis. Kaplan–Meier (KM) curve and time-dependent receiver operating characteristic curve (tROC) were used to evaluate the prognostic value and performance of MMGS, respectively. MMGS further verified its reliability and accuracy in the independent validation set. Finally, the characteristics of functional enrichment, tumor immune features, and inflammatory activity between different MMGS risk groups were also investigated.ResultsWe constructed a prognostic model consisting of six malignant cell maker genes (MAPT, C1QTNF4, MEG3, NPW, RAMP1, and CDT1), which stratified patients into ultra-high-risk (UHR) and common-high-risk (CHR) group. Patients in the UHR group had significantly worse overall survival (OS) than those in the CHR group. MMGS was verified as an independent predictor for the OS of HRNB patients. The area under the curve (AUC) values of MMGS at 1-, 3-, and 5-year were 0.78, 0.693, and 0.618, respectively. Notably, functional enrichment, tumor immune features, and inflammatory activity analyses preliminarily indicated that the poor prognosis in the UHR group might result from the dysregulation of the metabolic process and immunosuppressive microenvironment.ConclusionThis study established a novel six-malignant cell maker gene prognostic model that can be used to predict the prognosis of HRNB patients, which may provide new insight for the treatment and personalized monitoring of HRNB patients.

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Protein Tyrosine Phosphatases in Neuroblastoma: Emerging Roles as Biomarkers and Therapeutic Targets

Cited by 4 publications

References 205 publications

Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis

Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma

Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma

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