CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.     

PML Nuclear Bodies and SATB1 Are Associated with HLA Class I Expression in EBV+ Hodgkin Lymphoma

Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV− cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV− cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV− cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV− cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.     

Macrophage Polarization Reflects T Cell Composition of Tumor Microenvironment in Pediatric Classical Hodgkin Lymphoma and Has Impact on Survival

Macrophages have been implicated in the pathogenesis of classical Hodgkin lymphoma (cHL) and have been suggested to have a negative impact on outcome. Most studies addressing the role of macrophages in cHL have relied on identification of macrophages by generic macrophage antigens, e.g., CD68. We have therefore conducted an in situ analysis of macrophage polarization in a series of 100 pediatric cHL (pcHL) cases using double staining immunohistochemistry, combining CD68 or CD163 with pSTAT1 (M1-like) or CMAF (M2-like). M1- or M2-polarised microenvironment was defined by an excess of one population over the other (>1.5). Expression of STAT1 and LYZ genes was also evaluated by RT-qPCR. Patients <14 years and EBV+ cases displayed higher numbers of CD68+pSTAT1+ cells than older children and EBV- cases, respectively (P=0.01 and P=0.02). A cytotoxic tumor microenvironment, defined by a CD8+/FOXP3+ ratio >1.5 was associated with higher numbers of CD68+pSTAT1+ (P=0.025) and CD163+pSTAT1+ macrophages (P<0.0005). Levels of STAT1 and LYZ expression were associated with the numbers of CD68+pSTAT1+ macrophages. EBV+ cHL cases disclosed a predominant M1 polarized microenvironment similar to Th1 mediated inflammatory disorders, while EBV- cHL showed a predominant M2 polarized microenvironment closer to Th2 mediated inflammatory diseases. Better overall-survival (OS) was observed in cases with higher numbers of CD163+pSTAT1+ macrophages (P=0.02) while larger numbers of CD163+CMAF+ macrophages were associated with worse progression-free survival (PFS) (P=0.02). Predominant M1-like polarization as disclosed by CD163+pSTAT1+/CD163+CMAF+ ratio > 1.5 was associated with better OS (P= 0.037). In conclusion, macrophage polarization in pcHL correlates with prevalent local T cell response and may be influenced by the EBV-status of neoplastic cells. Besides, M1-like and M2-like macrophages displayed differential effects on outcome in pcHL.     

Elevated Soluble CD163 Plasma Levels Are Associated with Disease Severity in Patients with Hemorrhagic Fever with Renal Syndrome

Background

Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.

Methods

Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.

Results

The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.

Conclusion

sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.     

Beclin-1蛋白在霍奇金淋巴瘤中的表达及其临床意义

目的:探讨beclin-1蛋白在霍奇金淋巴瘤(Hodgkin lymphoma,HL)组织霍奇金里斯细胞(Hodgkin Reed-Sternberg,HRS)的表达及其与HL患者临床特征之间的关系.方法:收集2001年1月至2012年1月青岛大学医学院附属医院初发的HL患者61例和同期反应增生性淋巴结炎患者35例的组织标本为研究对象,通过免疫组化检测beclin-1蛋白在HL组织HRS细胞、反应性细胞及反应增生性淋巴结组织中的表达情况.结果:①HL与反应增生性淋巴结组织中beclin-1蛋白的阳性表达率分别为64％(39/61)和86 ％(30/35),HL组的beclin-1蛋白表达明显低于反应增生性淋巴结炎组,两者之间差异有统计学意义(P＜0.05);而在同一HL组织中,HRS细胞beclin-1蛋白的表达明显低于反应性细胞,差异有统计学意义(P＜0.05).②不同组织分型的HRS细胞beclin-1蛋白的表达有差异,淋巴细胞消减型(lymphocyte depletion,LD)HRS细胞beclin-1蛋白的表达明显低于混合细胞型(mixed cellularity,MC)及结节硬化型(nodular sclerosis,NS),差异有统计学意义(P＜0.05),富于淋巴细胞型(lymphocyte rich,LR)与混合细胞型、富于淋巴细胞型与结节硬化型、富于淋巴细胞型与淋巴细胞消减型、混合细胞型与结节硬化型之间HRS细胞beclin-1蛋白表达差异无统计学意义(P＞0.05).③HL组织中HRS细胞beclin-1蛋白表达水平与患者Ann Arbor分期、B症状及血清LDH值有关(P＜0.05),而与年龄、性别、巨大肿块及血沉无关(P＞0.05).结论:Beclin-1蛋白在HL中HRS细胞的表达明显降低,且与HL的恶性程度及侵袭性明显相关;beclin-1表达降低可能参与了HL发生发展.     

Macrophages and Dendritic Cells as Actors in the Immune Reaction of Classical Hodgkin Lymphoma

Background

The inflammatory infiltrate plays a pivotal role in classical Hodgkin lymphoma (cHL). Here, we focussed on the role of macrophages (MΦ) and dendritic cells (DC).

Methods

MΦ and DC infiltration was investigated in 106 cHL specimens using immunohistochemistry and cytokine expression was analyzed in a subset by real-time PCR. Human peripheral blood-derived monocytes, DC, MΦ stimulated with GM-CSF (MΦ^GM-CSF, pro-inflammatory MΦ-1-model) or M-CSF (MΦ^M-CSF, immunomodulatory MΦ-2-model) were incubated with cHL cell line (L1236, HDLM2) supernatants (SN). DC maturation or MΦ polarization were investigated by flow cytometry. Furthermore, the impact of DC or MΦ on cHL cell proliferation was analyzed by BrdU/CFSE assay.

Results

In cHL tissues mature myeloid (m)DC and MΦ predominated. High numbers of CD83+ mDC and low numbers of CD163+ MΦ were associated with improved disease specific survival. In numerous cHL specimens increased levels of both pro- and anti-inflammatory cytokines and of IL13 and GM-CSF were observed compared to reactive lymphadenopathies. Maturation of DC and induction and maintenance of an immunomodulatory MΦ phenotype were promoted by SN derived from cHL cell lines. TNFα neutralization in SN resulted in a significant inhibition of mDC maturation. DC and pro-inflammatory MΦ inhibited the proliferation of cHL cells.

Conclusion

Adopting an immunomodulatory phenotype is a potential mechanism for how MΦ promote immune evasion in cHL. Mature DC, in contrast, might participate in antitumoral immunity.     

Expression and Functional Relevance of Cannabinoid Receptor 1 in Hodgkin Lymphoma

Background

Cannabinoid receptor 1 (CB₁) is expressed in certain types of malignancies. An analysis of CB₁ expression and function in Hodgkin lymphoma (HL), one of the most frequent lymphomas, was not performed to date.

Design and Methods

We examined the distribution of CB₁ protein in primary cases of HL. Using lymphoma derived cell lines, the role of CB₁ signaling on cell survival was investigated.

Results

A predominant expression of CB₁ was found in Hodgkin-Reed-Sternberg cells in a vast majority of classical HL cases. The HL cell lines L428, L540 and KM-H2 showed strong CB₁-abundance and displayed a dose-dependent decline of viability under CB₁ inhibition with AM251. Further, application of AM251 led to decrease of constitutively active NFκB/p65, a crucial survival factor of HRS-cells, and was followed by elevation of apoptotic markers in HL cells.

Conclusions

The present study identifies CB₁ as a feature of HL, which might serve as a potential selective target in the treatment of Hodgkin lymphoma.     

Nitrotyrosine Level Was Associated with Mortality in Patients with Acute Kidney Injury

Background

To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI.

Methodology/Principal Findings

158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score.

Conclusions/Significance

There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness.     

Expression of Epstein-Barr Virus Nuclear Antigen 1 Is Associated with Enhanced Expression of CD25 in the Hodgkin Cell Line L428

Epstein-Barr virus is associated with several human malignancies including Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor α chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor β and γ chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.     

Expression of c-fos Was Associated with Clinicopathologic Characteristics and Prognosis in Pancreatic Cancer

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P<0.001). Besides, high cancerous c-fos expression was significantly associated with tumor site and T stage, whereas peri-neural invasion was of a borderline significant relevance. Log-rank test revealed that high expression of c-fos in cancer tissues was a significant marker of poor overall survival, accompanied by some conventional clinicopathologic variables, such as sex, grade, peri-neural invasion, T and N stages. More importantly, cancerous c-fos expression was identified as an independent prognosticator in multivariate analysis. Finally, the prognostic implication of c-fos expression was proven in four subsets of patients with PC. These data suggested that c-fos expression was of relationships with progression and dismal prognosis of PC.     

Disparities in Trace Metal Levels in Hodgkin/Non-Hodgkin Lymphoma Patients in Comparison with Controls

Biological Trace Element Research - Lymphoma arises from cells of the immune system and trace metals augment the immune system and their imbalance may promote immunological disorders including...     

Four Jointed Box 1 Promotes Angiogenesis and Is Associated with Poor Patient Survival in Colorectal Carcinoma

Angiogenesis, the recruitment and re-configuration of pre-existing vasculature, is essential for tumor growth and metastasis. Increased tumor vascularization often correlates with poor patient outcomes in a broad spectrum of carcinomas. We identified four jointed box 1 (FJX1) as a candidate regulator of tumor angiogenesis in colorectal cancer. FJX1 mRNA and protein are upregulated in human colorectal tumor epithelium as compared with normal epithelium and colorectal adenomas, and high expression of FJX1 is associated with poor patient prognosis. FJX1 mRNA expression in colorectal cancer tissues is significantly correlated with changes in known angiogenesis genes. Augmented expression of FJX1 in colon cancer cells promotes growth of xenografts in athymic mice and is associated with increased tumor cell proliferation and vascularization. Furthermore, FJX1 null mice develop significantly fewer colonic polyps than wild-type littermates after combined dextran sodium sulfate (DSS) and azoxymethane (AOM) treatment. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. Taken together our results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.     

T-Cell Responses Are Associated with Survival in Acute Melioidosis Patients

Background

Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design.

Methods

We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-γ) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43).

Results

We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN-γ cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-γ cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/μl.Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA_1c 10.2%, interquartile range 9.2–13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes.

Conclusions

The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as B. pseudomallei.     

The Clinical Significance of the CD163+ and CD68+ Macrophages in Patients with Hepatocellular Carcinoma

Our previous study has found that the abundance of peritumoral CD68⁺ macrophages was associated with poor prognosis in hepatocellular carcinoma (HCC) after resection. However, CD68 staining could not discriminate the protumoral or tumoricidal subpopulations from pan-macrophages. CD163 is a marker of alternatively activated macrophages. In this study, the clinical significance of CD163⁺ cells in tumors and peritumoral liver tissues was evaluated in a cohort of 295 patients with HCC after curative resection. We found that the density of CD163⁺ cells was well correlated with that of CD68⁺ cells in both tumors and peritumoral liver tissues but was much more. Immunostaining on consecutive sections and flow cytometry assay on surgical resected specimens further supported the findings that the CD163⁺ cells was more abundant than CD68⁺ cells. The density of peritumoral CD68⁺ cells was associated with poor recurrence-free survival (RFS) and poor overall survival (OS) (P = 0.004 and P = 0.001, respectively), whereas the CD163⁺ cells have no prognostic values either in tumors or in peritumoral liver tissues. In another cohort of 107 HCC patients, preoperative plasma concentration of soluble form of CD163 (sCD163) was associated with active hepatitis-related factors but not associated with the markers of tumor invasion. In conclusion, both the CD163⁺ cells local infiltration and plasma sCD163 were of limited significance in HCC, and they were more likely markers related to active hepatitis rather than tumor progression.     

The Expression of CD30 Based on Immunohistochemistry Predicts Inferior Outcome in Patients with Diffuse Large B-Cell Lymphoma

The prognostic value of CD30 expression indiffuse large B-cell lymphoma (DLBCL)remains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB) DLBCL, BCL-2 and Ki-67overexpression(p<0.05). Patients with CD30 expression showed significantly poor overall and event-free survivalcompared with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those with the high intermediate/high-risk international prognostic index (IPI)(p = 0.001 and 0.007, respectively). The prognostic value of CD30expression retained in DLBCL patients treated with eitherCHOP (cyclophosphamide, doxorubicin, vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysisrevealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively).In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcomein DLBCL patientstreated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.     

Extracellular Tumor-Related mRNA in Plasma of Lymphoma Patients and Survival Implications

Background

We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma.

Methodology/Principal Findings

mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA.

Conclusions/Significance

Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.     

Overexpression of CD97 Confers an Invasive Phenotype in Glioblastoma Cells and Is Associated with Decreased Survival of Glioblastoma Patients

Mechanisms of invasion in glioblastoma (GBM) relate to differential expression of proteins conferring increased motility and penetration of the extracellular matrix. CD97 is a member of the epidermal growth factor seven-span transmembrane family of adhesion G-protein coupled receptors. These proteins facilitate mobility of leukocytes into tissue. In this study we show that CD97 is expressed in glioma, has functional effects on invasion, and is associated with poor overall survival. Glioma cell lines and low passage primary cultures were analyzed. Functional significance was assessed by transient knockdown using siRNA targeting CD97 or a non-target control sequence. Invasion was assessed 48 hours after siRNA-mediated knockdown using a Matrigel-coated invasion chamber. Migration was quantified using a scratch assay over 12 hours. Proliferation was measured 24 and 48 hours after confirmed protein knockdown. GBM cell lines and primary cultures were found to express CD97. Knockdown of CD97 decreased invasion and migration in GBM cell lines, with no difference in proliferation. Gene-expression based Kaplan-Meier analysis was performed using The Cancer Genome Atlas, demonstrating an inverse relationship between CD97 expression and survival. GBMs expressing high levels of CD97 were associated with decreased survival compared to those with low CD97 (p = 0.007). CD97 promotes invasion and migration in GBM, but has no effect on tumor proliferation. This phenotype may explain the discrepancy in survival between high and low CD97-expressing tumors. This data provides impetus for further studies to determine its viability as a therapeutic target in the treatment of GBM.     

High Peritoneal Transport Status Was Not Associated with Mortality in Peritoneal Dialysis Patients with Diabetes

Background

Continuous ambulatory peritoneal dialysis (CAPD) patients with diabetes are at increased risk of mortality and high peritoneal transporters appear to contribute to poor survival. However, little is known about the combined impacts of high peritoneal transporters and diabetes on mortality.

Methods

This was a prospective observational cohort study. 776 incident CAPD patients were enrolled. Unadjusted and adjusted Cox proportional regression models were used to evaluate the association and interaction of peritoneal transport and diabetic status with mortality

Results

In the entire cohort, high peritoneal transport status was associated with an increased risk of all-cause mortality in unadjusted model [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.30 to 4.25, P = 0.01], but this association was not significant in multivariable model. There was an interaction between peritoneal membrane transport status and diabetes (P = 0.028). Subgroup analyses showed that compared to low and low average transporters, high transporters was associated with a higher risk of all-cause mortality (adjusted HR 1.78, 95% CI 1.07 to 4.70, P = 0.04) in CAPD patients without diabetes, but not in those with diabetes (adjusted HR 0.79, 95%CI 0.33 to 1.89, P = 0.59). Results were similar when transport status was assessed as a continuous variable.

Conclusions

The association between high peritoneal transport and all-cause mortality was likely to vary with diabetes status. High peritoneal transport was associated with an elevated risk of death among CAPD patients without diabetes, but not in those with diabetes.