Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas.

BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas. RNA-seq data of a cohort of 325 patients with glioma were available from the Chinese Glioma Genome Atlas and 671 from The Cancer Genome Atlas. R language, GraphPad Prism 5, and SPSS 22.0 were used to analyze data and draw figures. RESULTS: PTPN2 transcript levels increased significantly with higher grades of glioma and in isocitrate dehydrogenase (IDH) wild-type and mesenchymal subtype gliomas. A comprehensive biological analysis was conducted, which indicated a crucial role of PTPN2 in the immune and inflammation responses in gliomas. Specifically, PTPN2 was positively associated with HCK, LCK, MHC II, and STAT1 but negatively related to IgG and interferon. Moreover, canonical correlation analysis showed a positive correlation of PTPN2 with infiltrating immune cells, such as macrophages, neutrophils, and CD8+ T cells. Clinically, higher levels of PTPN2 were associated with a worse overall survival both in patients with gliomas and glioblastomas. CONCLUSION: PTPN2 expression level was increased in glioblastomas and associated with gliomas of the IDH wild-type and mesenchymal subtype. There was a close correlation between PTPN2 and the immune response and inflammatory activity in gliomas. Our results show that PTPN2 is a promising immunotherapy target and may provide additional treatment strategies.

The expression profile of PD-L1 and CD8+ lymphocyte in pituitary adenomas indicating for immunotherapy.

BACKGROUND: Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8+ tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs. METHODS: Immunohistochemistry (IHC) was performed to detect the expression of PD-L1 and CD8+ TILs in PAs. The ratio of positive expression of PD-L1 and CD8+ TILs was compared with chi-squared tests among different subtypes of PAs. The association between their expression profile and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. RESULTS: One hundred and ninety one patients with PAs were retrospectively involved in this study, consisting of 106 non-functioning PAs (NF-PAs, 55.5%), 40 PRL-secreting PAs (PRL-PAs, 20.9%), 31 GH-secreting PAs (GH-PAs, 16.2%), 9 ACTH-secreting PAs (ACTH-PAs, 4.7%) and 5 plurihormonal adenomas (2.6%) respectively. 36.6% of them were PD-L1 positive and 86.9% were CD8+ TILs positive. The positive PD-L1 immunostaining presented more frequently in functioning PAs (58.8%), compared with that (34.3%) in nonfunctioning group (p = 0.000). Moreover, the rates of PD-L1 expression were more associated with increased blood levels of PRL, GH, ACTH and cortisol. Contrastly, positive CD8+ TILs immunostaining was only correlated with elevated blood level of GH. For the analysis of immune markers with pathological results, PD-L1 expression was associated with PRL and GH immunostaining and higher Ki-67 index. But CD8+ TILs was only correlated with PRL immunostaining. CONCLUSION: Our results showed that PD-L1 was frequently expressed in functioning PAs with association of aggressive behaviors in PAs. The immunotherapy could be a promising treatment option of PAs.

[Multi-Spectral Polarized Properties of Ocean Aerosol].

In order to improve the retrieval accuracy of ocean aerosol , quantitative study was carried out in terms of the multi-spectral polarized properties of the aerosol in visible and near-infrared wavebands. Firstly, an aerosol model and a sea surface model were built. And the vector radiative transfer procedure of light in aerosol and atmosphere-ocean interface was simulated accurately based on the successive order of scattering method. Then from the perspective of the spectrum, the reflectance and polarized reflectance at the top of atmosphere in typical wavebands were quantitatively analyzed. Based on this, the spectrum distribution model of ocean aerosol polarized radiation was presented. And the model was validated with satellite data. Lastly, the influences of aerosol optical depth, viewing angle, chlorophyll a concentration and wind speed on multi-spectral polarized radiation of ocean aerosol were studied. The study shows that the changes of aerosol multi-spectral polarized radiation with wavelength can be best described with power function model when ignoring the absorbtion of atmosphere and solar flare effect in visible and near-infrared wavebands. This phenomenon can be caused by Rayleigh scattering and Mie scattering.The influences of chlorophyll a concentration and wind speed on multi-spectral polarized radiation of ocean aerosol emerge as very different in different wavebands. Specifically, the influences of chlorophyll a concentration on reflectance and polarized reflectance both can be neglected in near-infrared waveband. But in visible waveband, the influence on the reflectance must not be neglected any longer. Due to the increasement of the wind speed, the reflectance and the polarized reflectance increased significantly. But there are differences in the increases in different wavebands. The multi-spectral polarized radiative information of ocean aerosol can embody its own charactersitics effectively. And furthermore, the change of polarized reflectance with each factor has more obvious differences in different wavebands compared with reflectance. As a result, the multi-spectral polarized information of ocean aerosol can be used to retrieve the parameters of the aerosol over the ocean. The achievement of multi-spectral information has great significance for improving the retrieval accuracy of the ocean aerosol.

[Design of Dual-Beam Spectrometer in Spectrophotometer for Colorimetry].

Spectrophotometers for colorimetry are usually composed of two independent and identical spectrometers. In order to reduce the volume of spectrophotometer for colorimetry, a design method of double-beam spectrometer is put forward. A traditional spectrometer is modified so that a new spectrometer can realize the function of double spectrometers, which is especially suitable for portable instruments. One slit is replaced by the double-slit, than two beams of spectrum can be detected. The working principle and design requirement of double-beam spectrometer are described. A spectrometer of portable spectrophotometer is designed by this method. A toroidal imaging mirror is used for the Czerny-Turner double-beam spectrometer in this paper, which can better correct astigmatism, and prevent the dual-beam spectral crosstalk. The results demonstrate that the double-beam spectrometer designed by this method meets the design specifications, with the spectral resolution less than 10 nm, the spectral length of 9.12 mm, and the volume of 57 mm x 54 mm x 23 mm, and without the dual-beam spectral overlap in the detector either. Comparing with a traditional spectrophotometer, the modified spectrophotometer uses a set of double-beam spectrometer instead of two sets of spectrometers, which can greatly reduce the volume. This design method can be specially applied in portable spectrophotometers, also can be widely applied in other double-beam spectrophotometers, which offers a new idea for the design of dual-beam spectrophotometers.

[Sub-field imaging spectrometer design based on Offner structure].

To satisfy imaging spectrometers's miniaturization, lightweight and large field requirements in space application, the current optical design of imaging spectrometer with Offner structure was analyzed, and an simple method to design imaging spectrometer with concave grating based on current ways was given. Using the method offered, the sub-field imaging spectrometer with 400 km altitude, 0.4-1.0 microm wavelength range, 5 F-number of 720 mm focal length and 4.3 degrees total field was designed. Optical fiber was used to transfer the image in telescope's focal plane to three slits arranged in the same plane so as to achieve subfield. The CCD detector with 1 024 x 1 024 and 18 microm x 18 microm was used to receive the image of the three slits after dispersing. Using ZEMAX software optimization and tolerance analysis, the system can satisfy 5 nm spectrum resolution and 5 m field resolution, and the MTF is over 0.62 with 28 lp x mm(-1). The field of the system is almost 3 times that of similar instruments used in space probe.

Development and Validation of a Nomogram Model Based on Hematological Indicators for Predicting the Prognosis of Diffused Gliomas.

Background: Diffused gliomas are aggressive malignant brain tumors. Various hematological factors have been proven to predict the prognosis of patients with gliomas. The aim of this study is to integrate these hematological markers and develop a comprehensive system for predicting the prognosis of patients with gliomas. Method: This retrospective study included 723 patients pathologically diagnosed with diffused gliomas. Hematological indicators were collected preoperatively, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), albumin globulin ratio (AGR), platelet distribution width (PDW), red blood cell distribution width (RDW), fibrinogen (FIB), and prognostic nutritional index (PNI). Least absolute shrinkage and selection operator (LASSO) Cox was applied to screen the hematological indicators for a better prediction of patients' prognosis and to build an inflammation-nutrition score. A nomogram model was developed to predict the overall survival (OS), which included age, tumor grade, IDH-1 mutations, and inflammation-nutrition score. Result: Patients were randomly divided into a primary cohort (n = 509) and a validation cohort (n = 214). There was no difference in age and IDH-1 mutation frequency between the cohorts. In the primary cohort, NLR, LMR, AGR, FIB, and PNI were selected to build an inflammation nutrition score. Patients with a high-risk inflammation-nutrition score had a short median OS of 17.40 months compared with 27.43 months in the low-risk group [HR 2.54; 95% CI (1.91-3.37); p < 0.001]. Moreover, age, tumor grade, IDH-1 mutations, and inflammation-nutrition score were independent prognostic factors in the multivariate analysis and thus were included in the nomogram model. The nomogram model showed a high prediction value with a Harrell's concordance index (C-index) of 0.75 [95% CI (0.72-0.77)]. The validation cohort supported these results. Conclusion: The prognostic nomogram model provided a high prognostic predictive power for patients with gliomas.

[Spectral line shift property of prism dispersive imaging spectrometer].

In order to study the spectral line shift property of prism-dispersive imaging spectrometer, the influencing factors and mechanisms of spectral line shift were presented, and the mathematical model based on linear optics model was established to describe the spectral line shift property. Code V API functions was used, in Matlab environment, to verify the validity of mathematical model, and the sensitivity coefficient of spectral line shift was analyzed. Results indicate that rigid body motion of optical mirror surface generated by environmental variation is the key causation of spectral line shift. When the decenter of mirror surface is no more than 0.2 mm and the tilt is less than 0.02 degrees, the value of spectral line shift of different wavelengths at different fields is equivalent, and the error is less than 0.1 pixel. Spectral line shift due to mirror rigid body motion is linear and independent, and the total shift of the spectral line is the algebraic sum of values produced by the single freedom of motion (DOF) of single mirror surface. The mathematical model based on linear optics model can be used to study the spectral line shift property of the prism-dispersive imaging spectrometer. It will provide some guidance for spectral calibration and spectral property analysis under complex work condition.

Typical subdural contrast effusion secondary to endovascular treatment of a pediatric pial arteriovenous fistula.

Subdural contrast effusion secondary to endovascular treatment is exceptionally rare and might be mistaken as subdural hematoma because of similar hyperattenuation on computer tomography. The authors present the case of a 13-month-old girl with a history of increased head circumference and developmental retardation. Cerebral digital subtraction angiography showed a high-flow pial arteriovenous fistula fed by multiple arteries on the right cerebellar surface, with occlusion of the right sigmoid sinus and severe stenosis of the left sigmoid sinus. Staged endovascular treatments were performed to eliminate the fistula. Follow-up head computer tomography scans performed 3 h after both procedures demonstrated typical high-density subdural effusion with computer tomography attenuation value similar to hemorrhage. These effusions did not aggravate the condition and disappeared spontaneously 32 h after the first treatment and 29 h after the second, respectively.

Alterations in the RTK/Ras/PI3K/AKT pathway serve as potential biomarkers for immunotherapy outcome of diffuse gliomas.

BACKGROUND: Diffuse gliomas are the most common malignant brain tumors, and immune checkpoint inhibitors have limited therapeutic effects against this cancer. Three oncogenic pathways are altered in diffuse gliomas: the RTK/Ras/PI3K/AKT signaling, TP53, and RB pathways. Although these pathways may affect the tumor immune microenvironment, their association with immunotherapy biomarkers remains unclear. METHODS: We used copy number variation and mutation data to stratify patients with specific oncogenic signaling alterations, and evaluated their correlation with predictive immunotherapy biomarkers, including tumor mutation burden (TMB), immune cytolytic activity (CYT), tumor purity, and tumor-infiltrating CD8+ T cells. Immune checkpoint expression and interferon-γ signaling activity were also compared in these samples. RESULTS: We identified differentially expressed genes in three distinct oncogenic pathways. Gene ontology analysis of these genes revealed the involvement of RTK/Ras/PI3K/AKT-associated genes in immune and inflammatory responses. Moreover, significantly elevated TMB, CYT, and numbers of CD8+ T cells and decreased tumor purity were correlated with altered RTK/Ras/PI3K/AKT signaling. Single cell sequencing also confirmed that this tumor subgroup had increased immune checkpoint expression and interferon-γ signaling activity. Immune phenotyping based on the presence of CD274 and TMB or CD274 and CD8 T+ cells indicated that tumors with altered RTK/Ras/PI3K/AKT pathways represent a beneficial subtype and are associated with improved survival. CONCLUSION: Altered RTK/Ras/PI3K/AKT signaling and immunotherapy biomarkers are strongly correlated in gliomas. Gliomas with altered expression of RTK/Ras/PI3K/AKT pathway components may be sensitive to immunotherapy. A combination of small-molecule kinase inhibitors and immunotherapy is proposed for this subgroup of tumors.

[Stray light of space-borne hyperspectral imager and its measurement].

Hyperspectral imager has more spectral channels and higher spectral resolution compared to normal spectral instrument. Stray light is one of the important reasons affecting the spectral accuracy of the hyperspectral imager, but the current stray light measurements can't meet the need. Definition, sources and harmfulness of stray light are described in the present paper. The feasibility and superiority of the stray light factor d(i,j), used to describe the stray light characteristics of the spectral instruments, is investigated thoroughly, where the definition, physical significance and value of engineering application of stray light interference factor fi(lamda) and stray light disturbance factor Fi(lamda) are given. Finally, the system components, measurement procedure and measurement results of the stray light measurement system, using narrow-band filter, are introduced. Results show that the stray light factor d(i,j) meets the need of the stray light measurement because it can indicate the stray light characteristics of the spectral instruments without relationship to the light source, filter, detector and other measurement conditions, and the measurement efficiency is increased at least one-fold than the spectral stray light factors method.

Increased serum nesfatin-1 levels in patients with acromegaly.

Nesfatin-1 was identified as a satiety factor involved in the regulation of metabolism. Altered levels of circulating nesfatin-1 had been observed in a variety of diseases characterized by energy imbalance. However, there was no published data about nesfatin-1 levels in acromegaly.We evaluated serum nesfatin-1 levels in 13 patients with acromegaly at baseline and postoperatively, and in 21 age- and body mass index (BMI)-matched healthy subjects.Compared with the healthy subjects, patients with acromegaly had significantly increased levels of serum insulin, high-density lipoprotein cholesterol, triglyceride, and growth hormone (GH). Moreover, the acromegaly group had nesfatin-1 levels higher than controls (1.96 ±â€Š0.56 ng/mL vs 0.61 ±â€Š0.10 ng/mL, P = .004). There was a positive correlation of serum nesfatin-1 levels with diastolic blood pressure (r = 0.579, P = .038) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.598, P = .031) in patients with acromegaly. While a successful surgery decreased serum GH levels, the serum nesfatin-1 levels did not change in acromegaly (P = .965). At last, we compared serum GH/nesfatin-1 levels with predictive markers for aggressive behaviors in pituitary adenomas. There was no relationship between serum nesfatin-1 levels and tumor's size, Ki-67 index, mutant p53, or MGMT proteins. However, increased serum GH levels were positively correlated with tumors' size (P = .023) and mutant p53 proteins expression (P = .028).Circulating nesfatin-1 was increased in acromegaly, which was involved in metabolism regulation.

The prognostic role of Ki-67/MIB-1 in meningioma: A systematic review with meta-analysis.

BACKGROUND: Ki-67 is a typical immunohistochemical marker for cell proliferation. Higher expression of Ki-67 is correlated with poor clinical outcomes in several cancers. However, the prognostic value of Ki-67 on the prognosis of meningiomas is still controversial. The purpose of this meta-analysis was to evaluate the prognostic value of Ki-67 in meningiomas. METHODS AND MATERIALS: We searched Medline and EMBASE from inception to December 31, 2018, to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) for overall survival (OS) and disease/progression/recurrence-free survival (D/P/RFS) were estimated. RESULTS: A total of 43 studies, comprising 5012 patients, were included in this analysis. Higher Ki-67 expression levels were significantly associated with worse OS (HR = 1.565; 95% CI: 1.217-2.013) and D/P/RFS (HR = 2.644; 95% CI: 2.264-3.087) in meningiomas. Subgroup analysis revealed that all the included factors (ethnicity, tumor grade, HR sources, definition of cutoffs, cutoff values) for heterogeneity investigation can affect the pooled results. Among them, the definitions of cutoffs and cutoff values factor are the two main contributors toward heterogeneity. Multivariable meta-regression analysis also showed that methodologies used for cutoff value definition contributed to the high inner-study heterogeneity. CONCLUSIONS: Higher Ki-67 expression levels negatively influenced survival in meningiomas. A higher cutoff value (>4%) is more appropriate for prognosis prediction. It is highly recommended that Ki-67 expression profile could be assessed in meningiomas treatment for predicting survival. And patients with elevated expression of Ki-67 need to have close follow-ups.

Neutrophil depletion enhances the therapeutic effect of PD-1 antibody on glioma.

Tumor-infiltrating neutrophils (TINs), the predominant leukocytes in the tumor microenvironment, are important for cancer-related immunosuppression. Combinations of multiple immune checkpoint inhibitors can significantly improve outcomes in murine glioma models. Here, we investigated TIN levels in human glioma samples and tested the antitumor efficacy of neutrophil depletion alone or in combination with an anti-programmed death 1 (PD-1) antibody. To investigate the clinical relevance, we determined the correlation between tumor grade or survival and TIN levels in 202 resected glioma specimens. TCGA and CGGA data were used to validate the results and analyze the biological functions of TINs in gliomas. An orthotopic xenograft glioma mouse model was used to study the therapeutic effect of anti-PD-1 and/or anti-ly6G. Decreased TIN levels correlated with lower grades, mutant isocitrate dehydrogenase, and favorable prognosis, which was validated by CGGA and TCGA dataset results. Bioinformatics analysis revealed that TINs are mainly involved in angiogenic, inflammatory, and interferon-γ responses in gliomas. TINs were positively correlated with programmed death ligand-1 expression. In xenograft models, combined anti-PD-1 and neutrophil depletion therapy significantly inhibited tumor growth and promoted survival. This study demonstrates that TINs were related to glioma tumorigenesis. Targeting neutrophils could thus enhance the therapeutic effect of PD-1 blockade for gliomas.

Prognostic role of pretreatment red blood cell distribution width in patients with cancer: A meta-analysis of 49 studies.

Red blood cell distribution width (RDW) has been recently demonstrated to be a predictor of inflammation. High pretreatment RDW level is associated with poor survival outcomes in various malignancies, although the results are controversial. We aimed to investigate the prognostic role of RDW. A systematic literature search was performed in MEDLINE and EMBASE till April 2018. Pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). 49 studies with 19,790 individuals were included in the final analysis. High RDW level adversely affected both OS and DFS/PFS/RFS. For solid cancers, colorectal cancer (CRC) had the strongest relationship with poor OS, followed by hepatic cancer (HCC). Negative OS outcomes were also observed in hematological malignancies. Furthermore, patients at either early or advanced stage had inverse relationship between high pretreatment RDW and poor OS. Studies with cut-off values between 13% and 14% had worse HRs for OS and DFS/PFS/RFS than others. Furthermore, region under the curve (ROC) analysis was used widely to define cut-off values and had relatively closer relationship with poorer HRs. In conclusion, our results suggested that elevated pretreatment RDW level could be a negative predictor for cancer prognosis.

Sanbo Scoring System, Based on Age and Pre-treatment Hematological Markers, is a Non-invasive and Independent Prognostic Predictor for Patients with Primary Glioblastomas: A Retrospective Multicenter Study.

Various hematological markers are associated with survival in patients with glioblastomas (GBMs), as they reflect inflammation and nutrition status. However, single markers are insufficient for predicting prognosis in GBM, and a comprehensive scoring system is needed. In this study, we developed a simple, inexpensive, and non-invasive scoring system, referred to as the Sanbo Scoring System (SSS), to predict survival in patients with GBMs. Patients with GBM were retrospectively assigned to two independent cohorts at Sanbo Brain Hospital and National Cancer Center/Cancer Hospital. Clinical records, including age, routine blood tests, biochemistry and coagulation examinations, and IDH-1 status, were collected. In total, 274 and 87 patients with GBMs at Sanbo Brain Hospital and National Cancer Center/Cancer Hospital were included as derivation and validation cohorts, retrospectively. We developed the SSS based on data for the derivation cohort, i.e., age, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin-to-globulin ratio (AGR), and fibrinogen levels. These patients were divided into three groups that differed with respect to age, inflammation-nutrition status, and overall survival (p < 0.001), i.e., SSS 0, 1, and 2. NLR, PLR, and fibrinogen levels were lower and AGR was higher in the SSS 2 group than in the other groups, indicating better inflammation and nutrition statuses. Additionally, the longest overall survival was observed in this group. A multivariate analysis showed that SSS was an independent prognostic factor. The validation cohort supported all the results. SSS was a simple, non-invasive, and effective scoring system, and independently predicted survival in GBMs.

Diagnosis and treatment of pituitary microadenoma: report of 80 cases.

OBJECTIVE: To analyse and discuss the diagnosis and treatment of pituitary microadenoma. SUBJECTS AND METHODS: Eighty cases of pituitary microadenoma treated with transsphenoidal approach in our department were analysed retrospectively during the last 2 years. RESULTS: During following-up of 13.0+/-3.2 months, neither remained tumor was found except one patients with microprolactinoma, nor recurrence. Diabetes insipidus occurred in 19 patients, among which 15 patients recovered in 1 week, three in 1 month and one in 7 months. The adrenocorticotrophic hormone deficiency was found in nine of 63 patients with PRL-, GH- and non-functioning microadenoma (12%), but hypoadrenalemia recovered in all patients. Among these nine patients, seven recovered in 3 months and two in 6 months. Dysosphesia occurred in 32 cases: 30 recovered in 1 month and two in 4 months. Thirteen of 15 patients (86.7%) with ACTH-secreting microadenoma achieved chemical remission judged by plasma cortisol levels

Clinical significance of prognostic nutritional index in patients with glioblastomas.

Preoperative prognostic nutritional index (PNI) has been proven to be associated with clinical outcomes in patients with malignancies. However, data regarding the role of PNI in human glioblastomas (GBMs) is lacking. We, therefore, aimed to investigate the association between PNI and clinical parameters and survival in GBM patients.This retrospective analysis included 300 GBM patients who were surgically treated at our institute from 2008 to 2017. PNI was calculated as albumin (g/L) + 5×total lymphocyte count (10/L). SPSS 22.0, GraphPad Prism 5, and X tile were the primary tools used for data analysis, figuring drawing, and calculating optimal cutoffs, respectively.Mean albumin value, lymphocyte count, and PNI were 42.13 ±â€Š4.43 g/L, 1.73 ±â€Š0.71 × 10/L, and 50.80 ±â€Š6.01, respectively. PNI was increased in patients aged ≤60 years and in men. Moreover, PNI ≥44 was associated with improved overall survival in younger patients and women. PNI was not associated with isocitric dehydrogenase (IDH)-1 mutations or predicted survival in GBM patients without such mutations. Univariate analysis showed that a high preoperative Karnofsky performance score, gross total resection, completed chemoradiotherapy, IDH-1 mutations, and higher PNI levels were associated with favorable outcomes. Multivariate analysis showed that only completed chemoradiotherapy and IDH-1 mutations were independent prognostic factors.Our results indicated that PNI is associated with age and sex in GBM patients but fails to provide independent prognostic values.

Higher Plasma Fibrinogen Levels are Associated with Malignant Phenotype and Worse Survival in Patients with Glioblastomas.

Preoperative plasma fibrinogen levels were associated with poor clinical outcomes in malignancies. There were few data about the prognostic value of plasma fibrinogen in glioblastomas (GBMs). The objective of our study was to investigate the association between fibrinogen and patients' clinicopathological factors and overall survival (OS). From 2008 to 2016, 315 patients with GBMs who had a surgical treatment at our institute, were retrospectively involved in this study. IDH (isocitrate dehydrogenase) mutations and ATRX (alpha thalassemia/mental retardation syndrome X-linked) loss were detected with IHC (Immunohistochemistry). The preoperative plasma fibrinogen levels ranged from 1.00 to 5.22 g/L, with a mean of were 2.57 g/L. There were increased levels of plasma fibrinogen in patients aged ≥ 65 years, secondary GBMs, IDH mutation (p = 0.033) and ATRX loss (p = 0.040). Moreover, the plasma fibrinogen level was the highest in the subtype of IDH-1R132H wildtype - ATRX expression, which showed a shorter OS compared to the group of IDH-1R132H mut and IDH-1R132H wildtype - ATRX loss (p = 0.001, log-rank test). ROC curves for fibrinogen and IDH-1R132H wildtype - ATRX expression was also plotted, and indicated a potential diagnostic value of fibrinogen in molecular pathology. Univariate analysis found that younger age, higher KPS (Karnofsky Performance Score), gross total resection, complete chemoradiotherapy, IDH-1R132H mutations and lower levels of fibrinogen were associated with favorable outcomes. Multivariate analysis proved that chemoradiotherapy, IDH-1R132H and fibrinogen were independent prognostic factors. In conclusion, plasma fibrinogen could predict clinical outcome and molecular subtype in GBMs.

Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: A meta-analysis of 40 studies.

Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor progression, mainly through immune suppression. Inverse correlations have been observed between MDSC levels and patient survival for various malignancies. The purpose of this meta-analysis was to evaluate the prognostic value of pretreatment circulating MDSCs. We searched MEDLINE and EMBASE from their inceptions to September 2017 to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). A total of 40 studies comprising 2721 were included. For solid tumors, high levels of pretreatment circulating MDSCs were significantly associated with worse OS (HR = 1.796, 95% CI = 1.587-2.032) and DFS/PFS/RFS (HR = 2.459, 95% CI = 2.018-2.997). Breast cancer showed the largest association between high MDSC levels and worse OS (pooled HR = 3.053). Elevated MDSCs were also associated with worse OS for mixed-stage tumors (pooled HR = 1.659) and advanced-stage tumors (pooled HR = 2.337). Furthermore, both monocytic-MDSCs (M-MDSCs) and granulocytic or polymorphonuclear (PMN-MDSCs) showed negative associations with survival outcomes. Overall, high levels of pretreatment circulating MDSCs negatively influenced survival in most cancers. Pretreatment circulating MDSCs should be taken into account to further improve prognostic evaluation and develop novel therapeutic strategies.

Preoperative Changes in Hematological Markers and Predictors of Glioma Grade and Survival.

Background: Preoperative hematological markers that indicate nutritional, coagulation, and inflammation statuses have prognostic value for gliomas. This study aimed to investigate hematological markers with regard to tumor grades, isocitrate dehydrogenase mutations (IDH), age, and sex in patients with gliomas. Methods: From 2008 to 2017, patients with a pathological diagnosis of glioma who underwent surgery were retrospectively enrolled in this study. Information from clinical records, including age, sex, preoperative experiment tests (routine blood tests, biochemistry, and coagulation examinations), pathological results, and IDH status, was collected. A univariable survival analysis was performed. Hematological factors such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte-ratio (PLR), and albumin-to-globulin (AGR) were calculated. The prognostic nutrition index (PNI) was calculated as 10 × serum albumin value (g/dl) + 0.005 × peripheral lymphocyte count (per mm3). Results: Our study included 706 patients. The univariate analysis showed that age, IDH-1, and hematological factors were all significantly associated with overall survival (OS) in patients with gliomas. Our results showed that inflammation markers (NLR, PLR, and fibrinogen) were positively associated with age, whereas AGR was negatively associated with age. The PLR was significantly increased, whereas the AGR and PNI were decreased in women with gliomas, as compared with men. We found that inflammation markers increased and nutrition markers decreased with gliomas grade. However, these hematological markers did not significantly differ with IDH status. NLR was the best single hematological marker for distinguishing glioblastoma (GBM) [0.684 (0.645-0.723)], IDH-wt GBM [0.672 (0.631-0.71)] from other gliomas subtypes. Combinations of age with PNI and age with AGR were the best predictors of GBM [0.750 (0.713-0.786)] and IDH-wt GBM [0.759 (0.719-0.798)], respectively. Conclusion: Preoperative hematological marker levels vary among glioma grades and have high predictive values for GBM.