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Detection of Early Prognostic Biomarkers for Metastasis of Ewing’s Sarcoma in Pediatric Patients

ABSTRACT: Ewing’s sarcoma (ES) is a highly aggressive bone tumor, and the second most prevalent pediatric bone malignancy. The presence of metastasis at diagnosis decreases the three-year survival rate to 20% and contributes to diminished prognosis. Researches are indispensable for the early characterization of the disease and prediction of metastatic-prone patients, through biomarkers identification. Moreover, there is currently no available data on ES utilizing non-biopsy samples, such as plasma. This study utilizes a proteomic analysis of Ewing's sarcoma patient’s plasma samples and biopsies. Initially, the ES group was compared with the control counterpart. In a next step, the ES arm was further stratified into either initially metastatic and non-metastatic, or poor and good chemotherapy responder groups to identify protein expression profiles that can predict metastatic proneness and chemotherapy response, respectively.

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ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Sameh Magdeldin

LAB HEAD: Sameh Magdeldin

PROVIDER: PXD035812 | Pride | 2023-12-19

REPOSITORIES: pride

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Project description:Human SARS-CoV-2 and avian IBV are highly contagious and deadly coronaviruses causing devastating respiratory diseases in human and chicken, respectively. Lacking effective therapies exacerbates the disease associated with SARS-CoV-2 and IBV infections. Thus, novel therapeutic agents are in demand for controlling viral transmission and disease progression. Mesenchymal stem cells secreted factors (secretome) proven to be safe and highly efficient alternative to stem cells in mesenchymal stem cell-based therapy (MSCT). The most favorable advantage of secretome is the bypass of the side effects of MSCT that include but not limited to tumorigenesis, immune rejection, and infection. In this study, we aimed to investigate the antiviral activities of human Wharton’s jelly mesenchymal stem cells secretome against SARS-CoV-2 and IBV infection. The half-maximal inhibitory concentrations (IC50), and cytotoxic concentration (CC50) values of hWJ-MSC secretome (hWJ-MSC-S) were determined in Vero-E6 cells. Virucidal, anti-adsorption, and anti-replication mechanisms of hWJ-MSC-S against SARS-CoV-2 and IBV infection were evaluated in vitro. In Ovo anti-IBV activity of hWJ-MSC-S was estimated using Specific pathogen-free (SPF) embryonated chicken eggs (ECEs). The antiviral efficacy of hWJ-MSC-S was determined in terms of reduction in viral infection. Protein composition of hWJ-MSC-S was analyzed by mass spectrometry analysis, and gene ontology of secretome proteins was evaluated. Our data showed hWJ-MSC-S to significantly inhibits infection of human SARS-CoV-2 and avian IBV with very low cytotoxicity and embryotoxicity profile. CC50 value of hWJ-MSC-S in Vero-E6 was 39200 µg/ml. IC50, SI values of hWJ-MSC secretome against SARS-CoV-2 were 166.6 µg/ml, and 235.29, respectively. Similarly, IC50, SI values of hWJ-MSC-S against IBV were 439.9 µg/ml, and 89.11, respectively. hWJ-MSC-S reduced PFU/ml of SARS-CoV-2 and IBV by > 90%. Antiviral mechanistic studies demonstrated that hWJ-MSC-S had >95% and >90% virucidal effects on SARS-CoV-2 and IBV infections, respectively. The anti-replication effect was approximately 87.33% against SARS-CoV-2 infection, and >90% against IBV infection. In ovo model, hWJ-MSC-S significantly inhibited IBV infection. At a concentration of 1000 µg/ml, hWJ-MSC-S reduced IBV titre from 763000 ± 32638 to 38.333 ± 6.0093 EID50/ml (>99% inhibition). Similarly, hWJ-MSC-S reduced IBV titer from 763000 ± 32638 to 1896 ± 926.1 EID50/ml (>97% inhibition) at a concentration of 500 µg/ml. In addition, 250 µg/ml concentration of hWJ-MSC-S reduce IBV titer from 763000 ± 32638 to 20380 ± 2885 EID50/ml (>96% inhibition). LC/MS-MS analysis revealed that biological processes of hWJ-MSC-S proteins were mostly related to Immunomodulatory effect. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibit viral infection. These findings could be utilized in future pre-clinical and clinical studies to develop an effective therapeutic against human COVID-19 and avian IB respiratory diseases using hWJ-MSC-S.

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	200120-1-1.wiff	Wiff
	200120-1-1.wiff.scan	Wiff
	200120-1-10.wiff	Wiff
	200120-1-10.wiff.scan	Wiff
	200120-1-10_searchgui_out.zip	Other

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Detection of Early Prognostic Biomarkers for Metastasis of Ewing’s Sarcoma in Pediatric Patients

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