This is a prospective and retrospective observational study. The primary objective is to identify new prognostic biomarkers for DLBCL patients in terms of progression-free survival (PFS) and able to add predictive capacity to recognized important clinical factors.
The secondary objectives are:
* to identify new biomarkers associated with overall survival (OS) and objective response rate (ORR) * to characterize tissue and circulating immune microenvironment of DLBCL patients by bulk and single cell transcriptomics; * to assess the correlation between the expression of immune checkpoint genes and mRNA signature; * to describe the mutational status of a panel of genes relevant to DLBCL pathogenesis;. * to assess the correlation between protein expression, mutational status and the messenger RNA (mRNA) signature. * to investigate the association between radiomic features obtained from PET images and patient and tumour characteristics and clinical outcomes (PFS, OS, ORR).
For each enrolled patient, immunohistochemical determinations will be performed: Cell of origin (COO) (Germinal Cell -GC- or activated B-cell - ABC- type according with Hans algorithm ), evaluation of cluster of differentiation antigen 20 (CD20), cluster of differentiation antigen 5 (CD5), cluster of differentiation antigen 10 (CD10), Bcl6, Bcl2 (cut off\>50%), Multiple Myeloma 1 / Interferon Regulatory Factor 4 protein (MUM1/IRF4), c-myc (cut off\>40%) and Ki67, fluorescence in situ hybridization (FISH) for c-myc and if rearranged, for Bcl2 e Bcl6 ). Moreover, paraffin embedded (FFPE) tumor specimens will be collected for RNA extraction and mRNA expression mutational and proteomics analysis, centralized at IRST-IRCCS.
New diagnosis of High grade Diffuse large B cell Lymphoma undergoing first line standard treatment;
Signed written informed consent;
Availability of FFPE sample.
Diagnosis of High grade Diffuse large B cell Lymphoma from 2011 to 2017;
Patients included in clinical trials.
Prospective cohort: All patients with diagnosis of DLBCL afferring referred to IRST-IRCCS, Oncology-Hematology Units of AVR, S. Orsola Hospital (Bologna). Retrospective cohort: Patients with diagnosis of DLBCL referred to IRST-IRCCS, from 2011 to 2017 for whom clinical data and FFPE samples are available.
Cohort
Other
Prospective cohort
Other interventionImmunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis
Retrospective cohort
Other interventionImmunohistochemical determinations: Cell of Origin (COO) (according with Hans algorithm), evaluation of Cluster of Differentiation (CD) (CD20, CD5, CD10), Bcl6, Bcl2 (cut off\>50%), MUM1/IRF4, c-myc (cut off\>40%) and Ki67, FISH for c-myc and if rearranged for Bcl2 e Bcl6. mRNA expression by Nanostring Single cell analysis Immune checkpoint expression Proteomic analysis Metabolic analysis Radiomic analysis
identification of new prognostic biomarkers
To identify new prognostic biomarkers for DLBCL patients that combined to clinical factors (IPI) are able to create a MMCI, predictive in terms of progression-free survival (PFS) of DLBCL patients.
identification of molecular and clinical parameters
to identify molecular and clinical parameters associated with overall survival (OS) and objective response rate (ORR)
characterization of tissue and circulating immune microenvironment
to characterize tissue and circulating immune microenvironment by bulk and single cell transcriptomics
immune checkpoint genes analysis
to assess the correlation between the expression of immune checkpoint genes and mRNA signatures
mutational status
describe the mutational status of a panel of genes relevant to DLBCL pathogenesis
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