Immune-related protein signature in serum stratify relapsed mantle cell lymphoma patients based on risk
(2020) In BMC Cancer 20(1).- Abstract
Background: Response to modern treatment strategies, which combine cytotoxic compounds with immune stimulatory agents and targeted treatment is highly variable among MCL patients. Thus, providing prognostic and predictive markers for risk adapted therapy is warranted and molecular information that can help in patient stratification is a necessity. In relapsed MCL, biopsies are rarely available and molecular information from tumor tissue is often lacking. Today, the main tool to access risk is the MCL international prognostic index (MIPI), which does not include detailed biological information of relevance for different treatment options. To enable continuous monitoring of patients, non-invasive companion diagnostic tools are needed... (More)
Background: Response to modern treatment strategies, which combine cytotoxic compounds with immune stimulatory agents and targeted treatment is highly variable among MCL patients. Thus, providing prognostic and predictive markers for risk adapted therapy is warranted and molecular information that can help in patient stratification is a necessity. In relapsed MCL, biopsies are rarely available and molecular information from tumor tissue is often lacking. Today, the main tool to access risk is the MCL international prognostic index (MIPI), which does not include detailed biological information of relevance for different treatment options. To enable continuous monitoring of patients, non-invasive companion diagnostic tools are needed which can further reduce cost and patient distress and enable efficient measurements of biological markers. Methods: We have assessed if serum-based protein profiling can identify immune related proteins that stratify relapsed MCL patients based on risk. Overall, 371 scFv targeting 158 proteins were assessed using an antibody microarray platform. We profiled patients (n = 44) who had been treated within the MCL6-Philemon trial combining targeted and immune-modulatory treatment. Results: The downstream processing led to the identification of the relapsed immune signature (RIS) consisting of 11 proteins with potential to stratify patients with long and short overall survival (OS). Moreover, in this population, MIPI alone failed to separate high, intermediate and low risk patients, but a combined index based on MIPI together with RIS, MIPIris, showed improved performance and significantly stratified all three risk groups based on OS. Conclusions: Our results show that addition of biological parameters to previous prognostic indices improves patient stratification among patients treated with BTK inhibitor triplet combination, particularly, in the identification of an extreme high risk group.
(Less)
- author
- Lokhande, Lavanya LU ; Kuci Emruli, Venera LU ; Kolstad, Arne ; Hutchings, Martin ; Räty, Riikka ; Jerkeman, Mats LU and Ek, Sara LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Biomarker discovery, Mantle cell lymphoma (MCL), Protein signature, Serum proteins
- in
- BMC Cancer
- volume
- 20
- issue
- 1
- article number
- 1202
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85097238012
- pmid:33287742
- ISSN
- 1471-2407
- DOI
- 10.1186/s12885-020-07678-4
- language
- English
- LU publication?
- yes
- id
- 799308d0-6480-4d07-abfd-838144d5879c
- date added to LUP
- 2020-12-15 07:35:01
- date last changed
- 2024-05-01 22:51:31
@article{799308d0-6480-4d07-abfd-838144d5879c,
abstract = {{<p>Background: Response to modern treatment strategies, which combine cytotoxic compounds with immune stimulatory agents and targeted treatment is highly variable among MCL patients. Thus, providing prognostic and predictive markers for risk adapted therapy is warranted and molecular information that can help in patient stratification is a necessity. In relapsed MCL, biopsies are rarely available and molecular information from tumor tissue is often lacking. Today, the main tool to access risk is the MCL international prognostic index (MIPI), which does not include detailed biological information of relevance for different treatment options. To enable continuous monitoring of patients, non-invasive companion diagnostic tools are needed which can further reduce cost and patient distress and enable efficient measurements of biological markers. Methods: We have assessed if serum-based protein profiling can identify immune related proteins that stratify relapsed MCL patients based on risk. Overall, 371 scFv targeting 158 proteins were assessed using an antibody microarray platform. We profiled patients (n = 44) who had been treated within the MCL6-Philemon trial combining targeted and immune-modulatory treatment. Results: The downstream processing led to the identification of the relapsed immune signature (RIS) consisting of 11 proteins with potential to stratify patients with long and short overall survival (OS). Moreover, in this population, MIPI alone failed to separate high, intermediate and low risk patients, but a combined index based on MIPI together with RIS, MIPI<sub>ris</sub>, showed improved performance and significantly stratified all three risk groups based on OS. Conclusions: Our results show that addition of biological parameters to previous prognostic indices improves patient stratification among patients treated with BTK inhibitor triplet combination, particularly, in the identification of an extreme high risk group.</p>}},
author = {{Lokhande, Lavanya and Kuci Emruli, Venera and Kolstad, Arne and Hutchings, Martin and Räty, Riikka and Jerkeman, Mats and Ek, Sara}},
issn = {{1471-2407}},
keywords = {{Biomarker discovery; Mantle cell lymphoma (MCL); Protein signature; Serum proteins}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cancer}},
title = {{Immune-related protein signature in serum stratify relapsed mantle cell lymphoma patients based on risk}},
url = {{http://dx.doi.org/10.1186/s12885-020-07678-4}},
doi = {{10.1186/s12885-020-07678-4}},
volume = {{20}},
year = {{2020}},
}