Biomarker Dynamics in B-cell Lymphoma: A Longitudinal Prospective Study of Plasma Samples Up to 25 Years before Diagnosis

Späth, Florentin; Wibom, Carl; Krop, Esmeralda; Johansson, Anders; Bergdahl, Ingvar A.; Vermeulen, Roel; Melin, Beatrice

doi:10.1158/0008-5472.can-16-2345

Cited by 16 publications

(19 citation statements)

References 39 publications

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“…Therefore any reported mediating effect for the marker itself should be interpreted as a proxy of the underlying biologic milieu that is captured by circulating levels of those molecules that is partly mediating the alleged associations. We observed strong associations between sCD23, sCD27, sCD30, and CXCL13 in blood samples collected up to 19 years before diagnosis and risk of BCL development, consistent with previous studies [8][9][10][11][12]28,29 . The associations between sCD23 levels and development of BCL subtype were the most stable associations in this study, particularly for CLL, which was significant even more than 9 years before BCL diagnosis.…”

Section: Discussionsupporting

confidence: 92%

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Hosnijeh

Kolijn

Casabonne

et al. 2020

Sci Rep

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Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

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Section: Discussionsupporting

confidence: 92%

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Hosnijeh

Kolijn

Casabonne

et al. 2020

Sci Rep

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“…A recent study by Späth et al . nested within the Northern Swedish Health and Disease Study cohort is, to our knowledge, the only other besides our own to use repeated samples, with samples collected an average of 8 years apart . In comparisons between repeated samples, a rise in serum levels of sCD27 and sCD30 was observed for cases, particularly those diagnosed within 3 years of the second sample collection, consistent with a disease‐induced effect.…”

Section: Discussionmentioning

confidence: 73%

Circulating sCD27 and sCD30 in pre‐diagnostic samples collected fifteen years apart and future non‐Hodgkin lymphoma risk

Purdue

Lan

Hoffman‐Bolton

et al. 2018

Intl Journal of Cancer

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Elevated serum sCD27 and sCD30 from a single banked sample have been associated with future non-Hodgkin lymphoma risk; however, the etiologic relevance of this finding is unclear. To address this question, we conducted a case-control study (235 cases, 235 controls) nested within the CLUE-I and CLUE-II cohorts, which enrolled participants in 1974 and 1989 respectively in Washington County, Maryland. Our study features a subset of 102 cases and 102 controls with two banked pre-diagnostic samples each, collected fifteen years apart. In analyses involving an individual sample per subject, both sCD27 and sCD30 were associated with NHL diagnosed up to 20 years later. In analyses involving repeated samples, cases were significantly more likely than controls to have higher analyte levels in the CLUE-II vs. CLUE-I sample for sCD27 (P = 0.006) but not sCD30 (P = 0.16). In joint analyses of dichotomized analyte levels in both samples, the strongest NHL association observed for sCD27 was for having below-median levels in CLUE-I and above-median levels in CLUE-II [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.4-9.2 vs. below-median levels in both). In joint analyses for sCD30, the strongest NHL association was observed for having above-median levels in both samples (OR 1.7, 95% CI 0.8-3.7), particularly for cases diagnosed>10 years after the CLUE-II sample (OR 2.4, 95% CI 0.9-6.7). Our findings suggest that sCD27 is a disease marker for NHL and add to the weight of evidence that elevated circulating sCD30 is a marker of increased NHL susceptibility. This article is protected by copyright. All rights reserved.

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“…During the past few years a number of studies reported on the ability of various biomarkers measured in the blood of apparently healthy subjects to predict the risk of future diagnosis of CLL [ 12 – 16 ]. These predictive biomarkers concern cell surface markers and mitochondrial DNA copy number and provide limited insight into cellular processes that precede clinical disease.…”

Section: Introductionmentioning

confidence: 99%

Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis

et al. 2017

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BackgroundB-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance.ResultsWe employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0–15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p < 0.05) as well as 2 miRNAs (FDR < 0.05) which were associated with the risk of future CLL. The majority of these signals have also been observed in clinical CLL, suggesting the presence in prediagnostic blood of CLL-like cells. Future CLL cases who, at enrollment, had a relatively low B-cell fraction (<10%), and were therefore less likely to have been suffering from undiagnosed CLL or a precursor condition, showed profiles involving smaller numbers of the same differential signals with intensities, after adjusting for B-cell content, generally smaller than those observed in the full set of cases. A similar picture was obtained when the differential profiles of cases with time-to-diagnosis above the overall median period of 7.4 years were compared with those with shorted time-to-disease. Differentially methylated genes of major functional significance include numerous genes that encode for transcription factors, especially members of the homeobox family, while differentially expressed genes include, among others, multiple genes related to WNT signaling as well as the miRNAs miR-150-5p and miR-155-5p.ConclusionsOur findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4117-4) contains supplementary material. Note to Editor: If Journal regulations permit, the Supplementary material should be available to all without any additional authorisation.

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Biomarker Dynamics in B-cell Lymphoma: A Longitudinal Prospective Study of Plasma Samples Up to 25 Years before Diagnosis

Cited by 16 publications

References 39 publications

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Circulating sCD27 and sCD30 in pre‐diagnostic samples collected fifteen years apart and future non‐Hodgkin lymphoma risk

Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis

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