ABSTRACT
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.
ABSTRACT
Background and objective: Acute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS. Methods: 484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort. Results: In the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03-1.33], monocytes/µl [HR: 1.13, 95% CI: 1.05-1.21], non-classical monocytes/µl [HR: 1.09, 95% CI: 1.02-1.16] and CD56high NK cells/µl [HR: 1.13, 95% CI: 1.05-1.21] were detected to decrease the survival probability of AIS, while Tregs/µl [HR:0.97, 95% CI: 0.95-0.99, p=0.004], BM/µl [HR:0.90, 95% CI: 0.85-0.95, p=0.023] and CD16+NK cells/µl [HR:0.93, 95% CI: 0.88-0.98, p=0.034] may have the protective effect. As for indicators' discriminative ability, the AUC for CD56highNK cells/µl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/µl, BM/µl, CD16+NK cells/µl, or lower levels of CD56highNK cells/µl, CTL (%), non-classical monocytes/µl, Monocytes/µl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively. Conclusion: Our study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS.