Predictive value of the monocyte-to-lymphocyte ratio in the diagnosis of prostate cancer.

ABSTRACT: It has been reported that inflammation and immune system are related to prostate cancer. The neutrophil-to-lymphocyte ratio (NLR), as well as the platelet-to-lymphocyte ratio (PLR), have already been proposed as new indices to help diagnose prostate cancer (PCa). However, the monocyte-to-lymphocyte ratio (MLR) with regard to PCa has rarely been mentioned.To investigate the capability of the MLR to predict PCa.Patients who were pathologically diagnosed with PCa in our hospital and healthy control subjects who conformed to the inclusion criteria were enrolled. Patient data were recorded, including age, complete blood counts, blood biochemistry, and serum prostate-specific antigen (PSA) levels. The differences in these data between the groups were analyzed and the diagnostic value of the MLR was compared with PSA.Our study included a total of 100 patients with PCa and 103 healthy control subjects. Patients with PCa presented with a significantly higher NLR, MLR, and PLR compared to control subjects. However, the hemoglobin and lymphocyte levels were lower (P < .05) in PCa patients. The area under the curve (AUC) of PSA and ratio of free/total serum prostate-specific antigen were 0.899 (95% confidence interval [CI]: 0.857-0.942) and 0.872 (95% CI: 0.818-0.926), respectively, while the AUC of the MLR was 0.852 (95% CI: 0.798-0.906), which was higher than that of the NLR, PLR, and any other blood parameters. Additionally, the optimal cut-off value of the MLR for PCa was 0.264, with a specificity of 87.4% and a sensitivity of 72.0%. An evaluation of the diagnostic value of MLR + PSA gave an AUC of 0.936 (95% CI: 0.902-0.970). However, the AUC of MLR + PSA + f/tPSA was 0.996 (95% CI: 0.991-1.000). The diagnostic value of MLR + NLR + PSA gave an AUC of 0.945 (95% CI: 0.913-0.977), and the specificity is 0.971.PSA remains the most important diagnostic indicator. MLR combined with PSA and f/tPSA has the higher predictive value than PSA. It suggests that MLR may be another good predictive indicator of PCa. It can help reduce the clinical false positive rate.

Data-Independent Acquisition-Based Quantitative Proteomics Analysis Reveals Dynamic Network Profiles during the Macrophage Inflammatory Response.

Understanding of the molecular regulatory mechanisms underlying the inflammatory response is incomplete. The present study focuses on characterizing the proteome in a model of inflammation in macrophages treated with lipopolysaccharide (LPS). A total of 3597 proteins are identified in macrophages with the data-independent acquisition (DIA) method. Bioinformatic analyses reveal discrete modules and the underlying molecular mechanisms, as well as the signaling network that modulates the development of inflammation. It is found that a total of 87 differentially expressed proteins are shared by all stages of LPS-induced inflammation in macrophages and that 18 of these proteins participate in metabolic processes by forming a tight interaction network. Data support the hypothesis that ribosome proteins play a key role in regulating the macrophage response to LPS. Interestingly, conjoint analyses of the transcriptome and proteome in macrophages treated with LPS reveal that the genes upregulated at both the mRNA and protein levels are mainly involved in inflammation and the immune response, whereas the genes downregulated are significantly enriched in metabolism-related processes. These results not only provide a more comprehensive understanding of the molecular mechanisms of inflammation mediated by bacterial infection but also provide a dynamic proteomic resource for further studies.

Exosomes Derived From Septic Mouse Serum Modulate Immune Responses via Exosome-Associated Cytokines.

Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.