Dataset Information

CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma.

ABSTRACT: B cell receptor (BCR) signalling is an important pathway in diffuse large B cell lymphoma (DLBCL). In response to BCR triggering, normal and malignant B cells secrete the chemokines CCL3 and CCL4 to attract accessory cells to the tissue microenvironment. We measured CCL3 and CCL4 serum concentrations in 102 patients with newly diagnosed DLBCL by enzyme-linked immunosorbent assay, investigated their prognostic impact and validated our findings in an independent cohort of 51 patient samples. We also tested CCL3 and CCL4 secretion by DLBCL cells, and the influence of BTK inhibitors on the secretion of these chemokines. High CCL3 (?40 pg/ml) serum concentrations correlated with higher international prognostic index, lactate dehydrogenase and ?2 microglobulin, as did CCL4 (?180 pg/ml) with advanced Ann Arbor stages. High CCL3 levels correlated with significantly shorter progression-free and overall survival. The in vitro studies demonstrated that activated B cell-like, but not germinal centre B cell-like DLBCL cells, secrete high levels of CCL3 and CCL4 after BCR triggering, which was exquisitely sensitive to BCR pathway inhibition. These findings support CCL3 and CCL4 protein concentrations as biomarkers for BCR pathway activation and prognosis in DLBCL.

SUBMITTER: Takahashi K

PROVIDER: S-EPMC4715651 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma.

Takahashi Koichi K Sivina Mariela M Hoellenriegel Julia J Oki Yasuhiro Y Hagemeister Fredrick B FB Fayad Luis L Romaguera Jorge E JE Fowler Nathan N Fanale Michelle A MA Kwak Larry W LW Samaniego Felipe F Neelapu Sattva S Xiao Lianchun L Huang Xuelin X Kantarjian Hagop H Keating Michael J MJ Wierda William W Fu Kai K Chan Wing C WC Vose Julie M JM O'Brien Susan S Davis Richard E RE Burger Jan A JA

British journal of haematology 20150911 5

B cell receptor (BCR) signalling is an important pathway in diffuse large B cell lymphoma (DLBCL). In response to BCR triggering, normal and malignant B cells secrete the chemokines CCL3 and CCL4 to attract accessory cells to the tissue microenvironment. We measured CCL3 and CCL4 serum concentrations in 102 patients with newly diagnosed DLBCL by enzyme-linked immunosorbent assay, investigated their prognostic impact and validated our findings in an independent cohort of 51 patient samples. We al ...[more]

PMID: 26358140

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Project description:The objective of the present study was to assess the levels of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine the associations between the cytokine levels, clinicopathological manifestations and patient prognosis. The study enrolled 49 patients with DLBCL, 11 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and 67 healthy controls from Zhejiang Provincial People's Hospital (Hangzhou, China) between January 2017 and January 2020. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were measured using flow cytometry. The IL-6, IL-10 and IFN-γ levels were significantly raised in patients with DLBCL compared with those in the healthy controls (P<0.05). The levels of IL-10 were significantly higher in patients with raised levels of circulating lactate dehydrogenase (P<0.05), while increases in both IL-6 and IL-10 were associated with raised C-reactive protein (CRP) levels, with IL-6 levels positively associated with those of serum CRP (P<0.01; r=0.66). Additionally, International Prognostic Index (IPI) risk stratification of patients with DLBCL was strongly associated with circulating IL-6 and IL-10 levels. Raised IL-6, IL-10 and TNF-α levels were linked with worse short-term treatment efficacies (P<0.05). Moreover, the accuracy of the model predicting short-term treatment response in patients with DLBCL, obtained using the support vector machine algorithm, was 81.63%. It was also found that raised serum IL-6 and IL-10 levels, together with reduced levels of IL-17, were associated with survival of <1 year in patients with DLBCL (P<0.05), although no significant link was found between cytokine levels and long-term overall survival. In conclusion, the serum levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ can potentially serve as biological indicators of DLBCL tumor immune status, and combined application with the IPI score can be a robust prognostic indicator in patients with DLBCL.

Project description:Objectives: Previous studies have reported the prognostic value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and systemic immune-inflammation index (SII). However, the prognostic performance of these indices in patients with testicular lymphoma has not yet been studied. This study was to systematically evaluate the role of NLR, PLR, LMR, and SII in predicting survival for patients with testicular diffuse large B-cell lymphoma. Methods: In this study, 28 patients with testicular diffuse large B-cell lymphoma were enrolled. We performed univariate and multivariate analyses to assess associations of indices incorporating blood cell counts with progression-free survival (PFS) and overall survival (OS). Results: The results of univariate analysis revealed that International Prognostic Index (IPI) score (p = 0.010, p = 0.034, respectively), NLR (p = 0.003, p = 0.025, respectively), and LMR (p = 0.004, p = 0.010, respectively) were significantly associated with PFS and OS. Lactic dehydrogenase (LDH) (p = 0.017), absolute neutrophil counts (p = 0.018), absolute monocyte counts (p = 0.001), and SII (p = 0.005) were significantly associated with the risk of disease progression, while ECOG performance status (p = 0.016) was shown to be related to the risk of death. In the multivariate analysis, NLR (HR 9.069, p = 0.001) and absolute monocyte counts (HR 37.076, p = 0.001) were shown to be independently associated with risk for disease progression, while LMR (HR 0.077, p = 0.028), and ECOG performance status (HR 20.013, p = 0.026) were proved to be independent predictors of OS. Conclusions: In conclusion, high absolute monocyte counts, high NLR and low LMR may indicate unfavorable prognosis in testicular diffuse large B-cell lymphoma patients. Since indices incorporating blood cell counts are low cost parameters, they may provide additional prognostic value beyond standard clinicopathological parameters. However, further studies are needed to confirm our findings.

Project description:Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction. A comprehensive analysis was performed to select significant survival‐related snoRNAs in DLBCL. Collectively, a prognostic signature based on three snoRNAs (SNORD1A, SNORA60, and SNORA66) was established for DLBCL patients. Also, we found snoRNA co‐expressed genes that were mostly involved in ribosome‐correlated pathways and processes, and the interaction of ribosomal proteins (RPL23, RPL10A) and p53.

Dataset Information

CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma.

Publications

CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma.

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