Research on lymphoma
Below are examples of two projects where samples from U-CAN were used for study of lymphoma.
Plasma proteome profiling of cardiotoxicity in patients with diffuse large B-cell lymphoma
Gunilla Enblad (Uppsala), Charlott Mörth (Uppsala)
Cardiac toxicity is a risk associated with doxorubicin treatment for diffuse large B-cell lymphoma (DLBCL). Although well-known heart failure biological markers as NTproBNP and Troponins may be helpful, there are limited ways to predict evolving cardiac or cardiovascular toxicity during treatment. New possibilities have arisen with the technology to analyze samples for patterns of proteins associated with cardiovascular disease. The OLINK Proximity Extension Assay is based on such technology.
We aimed to establish the incidence of cardiac and cardiovascular disease in DLBCL patients treated with doxorubicin and analyze whether there are proteins associated with pre-existing or emerging cardiac or cardiovascular disease. In 95 patients, 182 different proteins from OLINK panels, NTproBNP, TroponinI and CRP were assessed prior to, during and after treatment. For comparison, samples from 60 age- and gender- matched controls were obtained.
We observed higher prevalence of cardiovascular disease in patients compared to controls (33% in the DLBCL cohort and 5.0% in the controls). In the DLBCL cohort 23.2% got a new cardiovascular disease. 32.6% died during follow up, 4 out of cardiovascular disease. Two proteins, SPON-1 and IL-1RT1, were related to pre-existing and emerging cardiovascular disease in doxorubicin treated patients. SPON-1 correlated to pre-treatment cardiovascular disease. IL-1RT1 was associated to emerging cardiovascular disease.
If confirmed in larger cohorts, IL-1RT1 may emerge as a biomarker for risk of developing cardiovascular disease in DLBCL.
Prognostic impact of soluble CD163 in patients with diffuse large B-cell lymphoma
Heli Vajavaara (Helsinki), Gunilla Enblad (Uppsala), Sirpa Leppa (Helsinki)
CD163 is a marker of alternatively activated M2 type macrophages shed into serum as soluble CD163 (sCD163). Elevated sCD163 levels are associated with poor prognosis in various diseases, including different malignancies. We aimed to assess clinical utility of sCD163 levels in patients with diffuse large B-cell lymphoma (DLBCL).
We measured sCD163 levels prior to and during treatment, and at follow-up in two independent cohorts. First, we included 119 DLBCL patients treated in a Nordic phase II trial with dose-dense immunochemotherapy. Second, we included a population-based cohort of 125 DLBCL patients from the Swedish U-CAN biobank. Overall survival (OS) and progression-free survival (PFS) in relation to pre-treatment sCD163 levels were assessed. Samples from five healthy volunteers were used as controls.
Pre-treatment sCD163 levels in the trial cohort were higher in comparison to healthy controls. In both cohorts, sCD163 levels declined significantly in response to therapy. Furthermore, elevated sCD163 levels were predictive of worse outcome in both cohorts. Together, our results demonstrate that pre-treatment sCD163 levels are elevated, decrease in response to therapy and predict unfavorable survival in patients with DLBCL.