Risk classification and therapeutic response of Wilms Tumor investigated by metabolomic-based mass spectrometry

• Grant number: 22/14179-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2023
• End date: August 31, 2026
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Andréia de Melo Porcari
• Grantee: Pedro Henrique Godoy Sanches
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Wilms tumors (WT) are neoplasms corresponding to 80% of pediatric renal tumors. The Children Oncology Group (COG) recommends tumor resection, adjuvant chemotherapy (CT), and radiotherapy. WT is composed of blastema, epithelium, and stroma, and the predominance of blastema classifies patients as "high risk" and is related to the tumor's QT response. However, there are two types of blastema, one more responsive to currently used drugs and one resistant. Through metabolomics-based mass spectrometry (MS), this proposal aims to discriminate the profile of blastema cells concerning the tissue's response to QT. The search for classificatory molecular signatures will use tumor tissues and will be evaluated by two MS techniques: Liquid Chromatography coupled to MS(LC-MS) and Desorption Electrospray Desorption Ionization - MS Imaging (DESI-MSI). Therefore, tissues from 40 retrospective patients diagnosed with TW between 2000-2005, stored at the Boldrini Children's Center (CAAE: 18608519.2.0000.5376), as well as their clinical data will be evaluated. The chemical composition as a function of the response and risk classification will be modeled using regression and machine learning techniques such as LASSO (Least Absolute Shrinkage and Selection Operator). Our preliminary results suggests LC-MS metabolomics identifies WT in tissues with 92.8% sensitivity, 86.6% specificity, and accuracy >89.5%. The molecules point to the support of cell proliferation through antioxidant mechanisms, and lipogenesis by reprogramming lipid metabolism. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE LIMA, IASMIM LOPES; SILVA, ALEX AP. ROSINI; BRITES, CARLOS; MIYAGUTI, NATALIA ANGELO DA SILVA; MANSOLDO, FELIPE RAPOSO PASSOS; NUNES, SARA VAZ; SANCHES, PEDRO HENRIQUE GODOY; CATALDI, THAIS REGIANI; DE CARVALHO, CAROLINE PAIS; DA SILVA, ADRIANO REIS; et al. Mass Spectrometry-Based Metabolomics Reveals a Salivary Signature for Low-Severity COVID-19. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 22, p. 18-pg., 2024-11-01. (22/14179-1)

SANCHES, PEDRO H. GODOY; DE MELO, NICOLLY CLEMENTE; PORCARI, ANDREIA M.; DE CARVALHO, LUCAS MIGUEL. Integrating Molecular Perspectives: Strategies for Comprehensive Multi-Omics Integrative Data Analysis and Machine Learning Applications in Transcriptomics, Proteomics, and Metabolomics. BIOLOGY-BASEL, v. 13, n. 11, p. 21-pg., 2024-11-01. (22/14179-1)