Circulating and Tumor-Infiltrating Foxp3+ Regulatory T Cell Subset in Chinese Patients with Extranodal NK/T Cell Lymphoma

<p>Foxp3⁺ regulatory T lymphocytes (Tregs) usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3⁺ subset in peripheral blood mononuclear cells (PBMCs) and tumor tissues from extranodal NK/T cell lymphoma (ENKTL). Our study showed the percentage of Foxp3⁺ subset from PBMC was significantly higher than that of healthy individuals (P&#60;0.001). The Foxp3⁺ subset from PBMCs expressed CD45RO, CTLA4, GITR, CCR7, and had an IL-10^highIFN&#947;⁺TGF&#946;⁺IL-2^lowIL-17^low cytokine secreting phenotype. Interestingly, the existence of EBV antigen-specific CD8⁺Foxp3⁺ Tregs was discovered in ENKTL. Furthermore, the high density of Foxp3⁺ TILs was associated with improved progression-free survival (PFS) in ENKTL patients (P&#60;0.05). Collectively, our study implicates that EBV antigens could induce antigen-specific CD8⁺Foxp3⁺ Tregs in ENKTL, and Foxp3⁺ TILs is an independent factor for PFS in ENKTL.</p

Multi-dimensional conditional mutual information with application on the EEG signal analysis for spatial cognitive ability evaluation

This study aims to explore an effective method to evaluate spatial cognitive ability, which can effectively extract and classify the feature of EEG signals collected from subjects participating in the virtual reality (VR) environment; and evaluate the training effect objectively and quantitatively to ensure the objectivity and accuracy of spatial cognition evaluation, according to the classification results. Therefore, a multi-dimensional conditional mutual information (MCMI) method is proposed, which could calculate the coupling strength of two channels considering the influence of other channels. The coupled characteristics of the multi-frequency combination were transformed into multi-spectral images, and the image data were classified employing the convolutional neural networks (CNN) model. The experimental results showed that the multi-spectral image transform features based on MCMI are better in classification than other methods, and among the classification results of six band combinations, the best classification accuracy of Beta1–Beta2–Gamma combination is 98.3%. The MCMI characteristics on the Beta1–Beta2–Gamma band combination can be a biological marker for the evaluation of spatial cognition. The proposed feature extraction method based on MCMI provides a new perspective for spatial cognitive ability assessment and analysis

MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases

Abstract Aims MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. Methods MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. Results MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). Conclusions MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated

A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

BACKGROUND:Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS:A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively. RESULTS:Univariate analysis revealed that higher LMR level (≥ 5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥ 2.145 × 10(9)/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475 × 10(9)/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001), DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001) and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080). CONCLUSIONS:The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients

Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC). Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, P<0.001). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (all P<0.05). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493) in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC

Kaplan–Meier survival analysis of baseline LMR in NPC patients.

<p>A. OS curves for LMR; B. DFS curves for LMR; C. DMFS curves for LMR; D. LRRFS curves for LMR. LMR, lymphocyte-to-monocyte ratio; NPC, nasopharyngeal carcinoma; OS, overall survival; DFS, disease-free survival; DMFS, distant metastasis-free survival; LRRFS, loco-regional recurrence-free survival.</p

Multivariate analysis of independent prognostic factors for patients with nasopharyngeal carcinoma (n = 1547).

<p>Abbreviation: OS  =  Overall Survival; DFS  =  Disease-Free Survival; DMFS  =  Distant Metastasis-Free Survival; LRRFS  =  Loco-Regional Recurrence-Free Survival; CRT  =  chemoradiotherapy; RT  =  radiotherapy; LMR  =  lymphocyte-to-monocyte ratio; HR  =  Hazard Ratio, derived from COX proportional hazard model. In this analysis, T status, N status and tumor stage were divided into two groups. For T status: T1-2 and T3-4; for N status:N0-1 and N2-3; for tumor stage: I–II and III–IV.</p

Kaplan–Meier survival analysis of baseline lymphocyte count (LY) in NPC patients.

<p>A. OS curves for LY; B. DFS curves for LY; C. DMFS curves for LY; D. LRRFS curves for LY. LY, lymphocyte count; NPC, nasopharyngeal carcinoma; OS, overall survival; DFS, disease-free survival; DMFS, distant metastasis-free survival; LRRFS, loco-regional recurrence-free survival.</p

Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC. Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC). Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%, &lt; 0.001). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (all &lt; 0.05). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor ( = 0.022, hazard ratio = 1.635, 95% CI 1.073-2.493) in HNSCC patients. Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC