Gene-expression profiling in early and advanced-stage follicular lymphoma by microarray analysis: exploratory investigation of biomarkers predictors of prognosis

• Grant number: 20/13246-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Luís Alberto de Pádua Covas Lage
• Grantee: Luís Alberto de Pádua Covas Lage
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Cristiane Rúbia Ferreira ; Daniel Silva Nogueira ; Debora Levy ; Hebert Fabricio Culler ; Jessica Ruivo Maximino ; Juliana Pereira

Abstract

Follicular Lymphoma (FL) represents the second most common type of lymphoma after diffuse large B cell lymphoma (DLBCL) and 70% of all indolent lymphomas. Biological heterogeneity is a hallmark of the disease and determines both variable clinical behavior at initial presentation and aggressive clinical course. Those features may be due to clinical, genetic, epigenetic and tumor microenvironment factors. A better comprehension of the role of these features on the natural history of the disease is a great challenge to improve management of treatment and risk stratification. Hence, it may enable to identify new predictors of bad prognosis in the background of FL. The aim of this study is to evaluate the prognostic impact of gene expression profile (GEP) in early and advanced stage FL grades 1-3a at diagnosis compared to normal lymph node specimens by Microarray analysis. Clinical outcome measures will be performed for both groups. The primary objective of this study is to identify subgroups of patients with early stage (I e II) grades 1, 2 e 3a and advanced stage FL with low tumor burden and high risk of disease progression by investigation of GEP with microarray technique. Secondary objective is to identify subgroup of patients with advanced stage FL grades 1, 2 e 3a and high tumor burden/ presenting sympthoms treated with chemoimmunotherapy with high risk of progression within 24 months after the first treatment (POD24) by analysis of GEP with microarray. RNA extraction of high quality from Formalin-Fixed Paraffin-Embedded tumoral samples obtained at FL diagnosis randomly selected from 250 individuals from January 2000 to December 2020 at "Instituto do Cancer do Estado de Sao Paulo" and revised by an expert pathologist will be processed at the University of Sao Paulo Hospital Genomics Laboratory. Initial screening will be performed for gene expression profile assay using Microarray assay (Agilent Technology) in the Faculty of Medicine of University of Sao Paulo Hospital. The technique of qRT-PCR (real time polymerase chain reaction) will be applied for internal validation of study findings as well as external validation of GEP in another cohort. Survival analysis by Kaplan-Meier method will be performed and tested the association between GEP and clinical prognostic outcomes. (AU)