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Study of the Actin Cytoskeleton in Live Endothelial Cells Expressing GFP-Actin
Published on: November 18, 2011
Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma
Susanne Bram Ednersson1,2, Martin Stenson3,2, Mimmie Stern4,2
1Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Abstract:
Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1 year from diagnosis (REF/REL), and 53 who were progression-free more than 5 years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P = 7·6 × 10-10 ). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P = 1·4 × 10-9 ). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.
Insights
Diffuse large B cell lymphoma (DLBCL) patients with refractory or relapsed disease show distinct protein expression profiles. Overexpressed ribosomal proteins in refractory/relapsed DLBCL suggest potential therapeutic targets for improving treatment outcomes.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a poor prognosis.
- Immunochemotherapy resistance is a major cause of treatment failure in DLBCL.
- Understanding the molecular basis of resistance is crucial for developing new therapies.
Purpose of the Study:
- To identify global protein expression differences between refractory/relapsed and cured DLBCL patients.
- To uncover potential protein biomarkers associated with treatment resistance or sensitivity.
- To explore novel mechanisms underlying immunochemotherapy resistance in DLBCL.
Main Methods:
- Proteomic mass spectrometry was used to analyze formalin-fixed paraffin-embedded tumor tissues.
- Global protein expression was compared between 44 refractory/relapsed (REF/REL) DLBCL patients and 53 cured (CURED) DLBCL patients.
- Immunohistochemical staining was performed to validate key protein expression differences.
Main Results:
- A total of 2127 proteins were identified, with 102 differentially expressed between groups.
- Sixty-five proteins were overexpressed in REF/REL patients, including 46 ribosomal proteins (RPs).
- Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, contrasting with REF/REL patients.
Conclusions:
- Overexpression of ribosomal proteins in refractory/relapsed DLBCL may indicate a mechanism of immunochemotherapy resistance.
- Increased expression of actin-associated proteins in cured patients suggests a role in treatment sensitivity.
- These findings highlight potential new therapeutic targets and biomarkers for DLBCL treatment resistance.
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