Abstract
The prognosis of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains unsatisfactory and, despite major advances in genomic studies, the biological mechanisms underlying chemoresistance are still poorly understood. We conducted for the first time a large-scale differential multi-omics investigation on DLBCL patient’s samples in order to identify new biomarkers that could early identify patients at risk of R/R disease and to identify new targets that could determine chemorefractoriness. We compared a well-characterized cohort of R/R versus chemosensitive DLBCL patients by combining label-free quantitative proteomics and targeted RNA sequencing performed on the same tissues samples. The cross-section of both data levels allowed extracting a sub-list of 22 transcripts/proteins pairs whose expression levels significantly differed between the two groups of patients. In particular, we identified significant targets related to tumor metabolism (Hexokinase 3), microenvironment (IDO1, CXCL13), cancer cells proliferation, migration and invasion (S100 proteins) or BCR signaling pathway (CD79B). Overall, this study revealed several extremely promising biomarker candidates related to DLBCL chemorefractoriness and highlighted some new potential therapeutic drug targets. The complete datasets have been made publically available and should constitute a valuable resource for the future research.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma (NHL) and is a clinically and biologically heterogeneous disease
We performed for the first time a large-scale differential multi-omics study on diffuse large B-cell lymphoma (DLBCL) patient’s samples in order to search for new potential biomarkers that could help to early identify patients at risk of refractory or early-relapsed (R/R) disease and to better understand the biological mechanisms underlying chemorefractoriness
Fresh-frozen tumour tissues were collected at the time of diagnosis, before any treatment, for 8 chemorefractory and 12 chemosensitive DLBCL patients who were uniformly treated in first-line with rituximab and an anthracycline-based chemotherapy regimen in a single institution
Summary
Of DLBCL has been extensively studied, demonstrating the intratumoral heterogeneity and allowing the identification of recurrent somatic mutations, some of which provide promising opportunities for new drug developments[5]. No data are available in the literature focusing on the proteomic characterization of R/R DLBCL In this context, we conducted a large-scale differential proteomic investigation of R/R versus chemosensitive DLBCL patients in order to identify new potential biomarkers related to resistance to treatment and to better understand the biological mechanisms underlying chemoresistance. We conducted a large-scale differential proteomic investigation of R/R versus chemosensitive DLBCL patients in order to identify new potential biomarkers related to resistance to treatment and to better understand the biological mechanisms underlying chemoresistance This proteomic investigation was combined with a quantitative transcriptomics experiment performed on the same samples to correlate genes expression and their impact at the proteomic level
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