Differences in 1HNMR Based Metabolomic Patterns of Malignant and Benign Pleural Effusions.

OBJECTIVE: Malignant pleural effusion (MPE) is a common complication of lung cancer with poor prognosis. Benign pleural effusion (BPE), such as tuberculous and pneumonic pleural effusion, usually has a good prognosis. Differential diagnosis between MPE and BPE remains a clinical challenge. METHODS: 52 MPE, 93 BPE, and their corresponding serum samples were analyzed by hydrogen nuclear magnetic resonance (1HNMR) based metabolomics. RESULTS: The 1HNMR study showed that some amino acids and betaine in MPE are significantly altered in pleural effusion and serum compared to BPE patients. Levels of serum glucose and glutamine have strong positive correlation with those in pleural effusion (r>0.6) for MPE patients. The area under the receiver operating characteristic curve (AUROC) values of metabolites in pleural effusion or serum were less than 0.805 in differentiating MPE from BPE. Improved an AUROC value of 0.901 was observed using pleural effusion-serum ratios of glutamic acid in differentiating MPE from BPE, which was further validated by 15 double-blind samples. CONCLUSIONS: Compared with BPE patients, amino acids and betaine in MPE are significantly altered in pleural effusion and serum. Pleural effusion-serum ratio of glutamic acid may contribute to the rapid diagnosis of MPE from BPE by 1HNMR analysis.

Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

Can LENT Prognostic score (LDH, ECOG performance score, blood neutrophil/lymphocyte ratio, tumor type) change the clinical approach in malignant pleural effusion?

INTRODUCTION: The aim of this study was to evaluate the predictive power of LENT (LDH in pleural fluid, Eastern Cooperative Oncology Group [ECOG] performance status, neutrophil-lymphocyte ratio in the serum, and tumor type) score which is a current prognostic score in patients with MPE and to determine its effect on survival and its status in clinical decision making. In addition, it was aimed to compare LENT score with the conventional but subjective score ECOG. MATERIALS AND METHODS: A retrospective observational study was conducted reviewing the medical records of patients managed for MPE (malign pleural effusion) between 2008 and 2018. LENT prognostic score was calculated in the patients. The ECOG score calculated for the same patients was compared in terms of mortality. RESULT: A total of 191 patients with malignant pleural effusion, 118 males (61.7%) and 73 females (38.2%), were included in the study. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying overall survival were 69.8 %, 100%, 100% and 18.8%, respectively at the LENT score > 4 (p= 0.000). At ECOG PS >2, the sensitivity, specificity, PPV, NPV were as the same as the LENT score >4 for identifying overall survival. In all patients, overall median survival according to the LENT score was 662/119/33 days in low/moderate/high risk groups, respectively. Cox regression analysis indicated that having a moderate LENT score (p= 0.004, OR: 2.21, CI: 1.29 -3.78%) and high LENT score (p= 0.000, OR: 4, 50 CI: 2.57-7.89%) were predictors for overall survival in all patients due to MPE. In ROC analysis, there was no difference in mortality in erms of both LENT and ECOG at 1st, 6th and 12th months. CONCLUSIONS: LENT is a better scoring system than ECOG in predicting early mortality, while both ECOG and LENT have almost the same power in predicting mortality. However, LENT is slightly more objective but more difficult to calculate because it contains laboratory findings. Thus, both scoring systems can be used to predict mortality in patients with malignant pleural effusions. Neither of them has superiority to each other.

Using Disposable Membrane Cell Collector to Enrich Lung Adenocarcinoma Cells in Bloody Pleural Effusion for Anaplastic Lymphoma Kinase Fusion Gene Detection.

PURPOSE: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection. MATERIALS AND METHODS: CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results. RESULTS: The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed. CONCLUSIONS: Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.

Selection of microRNAs in extracellular vesicles for diagnosis of malignant pleural mesothelioma by in vitro analysis.

Malignant pleural mesothelioma (MPM) is a malignant tumor which is a challenge for diagnosis and is associated with a poor patient prognosis. Thus, early diagnostic interventions will improve the quality of life and life expectancy of these patients. Recently, cellular microRNAs (miRNAs) have been found to be involved in maintaining homeostasis, and abnormal miRNA expression has often been observed in various diseases including cancer. Extracellular vesicles (EVs) released by many cells contain proteins and nucleic acids. miRNAs are secreted from all cells via EVs and circulate throughout the body. In this study, culture media were passed sequentially through membrane filters 220­50 nm in size, and EVs with diameters of 50 to 220 nm (EVcap50/220) were collected. miRNAs (EV50­miRNAs) in EVcap50/220 were purified, and microarray analysis was performed. EV50­miRNA expression profiles were compared between MPM cells and a normal pleural mesothelial cell line, and six EV50­miRNAs were selected for further investigation. Of these, hsa­miR­193a­5p and hsa­miR­551b­5p demonstrated higher expression in MPM­derived EVcap50/220. These miRNAs reduced the expression of several genes involved in cell­cell interactions and cell­matrix interactions in normal pleural mesothelial cells. Our data suggest that hsa­miR­193a­5p and hsa­miR­551b­5p in EVcap50/220 could be diagnostic markers for MPM.

Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion.

BACKGROUND: Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio. PATIENTS AND METHOD: The study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators. RESULT: In the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (all p < 0.001). In the test set, PF CEA at the cut-off value of 5.23 ng/ml showed the highest sensitivity, specificity and accuracy, positive and negative predictive value among other tumor biomarkers, which were 99.0%, 69.1%, 91.6%, 90.7%, and 95.9%, respectively. CONCLUSION: PF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.

TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response.

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

Pro-cathepsin D as a diagnostic marker in differentiating malignant from benign pleural effusion: a retrospective cohort study.

BACKGROUND: Malignant pleural effusion (MPE) causes substantial symptomatic burden in advanced malignancy. Although pleural fluid cytology is a commonly accepted gold standard of diagnosis, its low diagnostic yield is a challenge for clinicians. The aim of this study was to determine whether pro-cathepsin D can serve as a novel biomarker to discriminate between MPE and benign pleural effusion (BPE). METHODS: This study included 81 consecutive patients with exudative pleural effusions who had underwent thoracentesis or pleural biopsy. Pleural fluid and serum were collected as a standard procedure for all individuals at the same time. The level of pro-cathepsin D was measured by the sandwich enzyme-linked immunosorbent assay method. RESULTS: Though there were no significant differences in plasma pro-cathepsin D between the two groups, the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group (0.651 versus 0.590 pg/mL, P = 0.034). The discriminative power of pleural fluid pro-cathepsin D for diagnosing MPE was moderate, with 81% sensitivity and 53% specificity at a pro-cathepsin D cut-off ≥0.596 pg/mL (area under the curve: 0.656). Positive and negative predictive values for MPE were 38 and 89%, respectively, with pro-cathepsin D cut-off value (> 0.596 pg/mL). CONCLUSIONS: The level of pleural fluid pro-cathepsin D was found to be significantly higher in MPE than in BPE. Although results of this study could not support the sole use of pleural fluid pro-cathepsin D to diagnose MPE, pleural fluid pro-cathepsin D can be added to pre-existing diagnostic methods for ruling-in or ruling-out MPE.

Pleural and serum markers for diagnosis of malignant pleural effusion.

BACKGROUND: Differentiation between benign and malignant exudative pleural effusion remains a clinical challenge. Recently, several markers have been reported to increase the diagnostic accuracy of malignant pleural effusion, with controversial results. METHODS: Patients with exudative pleural effusion were divided into 2 groups: a malignant pleural effusion group (39 patients) diagnosed by malignant cells in pleural fluid cytology or by malignant infiltration of the pleura on pleural biopsy, and a benign pleural effusion group (51 patients) with neither malignant cells in pleural fluid cytology nor malignant infiltration of the pleura on pleural biopsy. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were determined in both serum and pleural fluid samples, using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The etiology of malignant pleural effusion in the malignant group was breast cancer in 43.6% and bronchogenic carcinoma in 25.6%. There was a statistically significant difference between the 2 groups regarding sex, with more males in the benign group. There was no significant difference between groups regarding age. The median levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were higher in the malignant group than in the benign group, and the differences were highly significant in both pleural fluid (p < 0.001) and serum (p < 0.001). CONCLUSION: Matrix metaloproteinase-9 and tissue inhibitor of metalloproteinase-1 in serum and pleural fluid samples might be valuable markers for differentiating benign from malignant pleural effusions.

Development and validation of a novel scoring system developed from a nomogram to identify malignant pleural effusion.

BACKGROUND: This study aimed to establish and validate a novel scoring system based on a nomogram for the differential diagnosis of malignant pleural effusion (MPE) and benign pleural effusion (BPE). METHODS: Patients with PE and confirmed aetiology who underwent diagnostic thoracentesis were included in this study. One retrospective set (N = 1261) was used to develop and internally validate the predictive model. The clinical, radiological and laboratory features were collected and subjected to logistic regression analyses. The primary predictive model was displayed as a nomogram and then modified into a novel scoring system, which was externally validated in an independent set (N = 172). FINDINGS: The novel scoring system was composed of fever (3 points), erythrocyte sedimentation rate (4 points), effusion adenosine deaminase (7 points), serum carcinoembryonic antigen (CEA) (4 points), effusion CEA (10 points) and effusion/serum CEA (8 points). With a cutoff value of 15 points, the area under the curve, specificity and sensitivity for identifying MPE were 0.913, 89.10%, and 82.63%, respectively, in the training set, 0.922, 93.48%, 81.51%, respectively, in the internal validation set and 0.912, 87.61%, 81.36%, respectively, in the external validation set. Moreover, this scoring system was exclusively applied to distinguish lung cancer with PE from tuberculous pleurisy and showed a favourable diagnostic performance in the training and validation sets. INTERPRETATION: This novel scoring system was developed from a retrospective study and externally validated in an independent set based on six easily accessible clinical variables, and it exhibited good diagnostic performance for identifying MPE. FUNDING: NFSC grants (no. 81572942, no. 81800094).

Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition.

Malignant pleural effusion (MPE) confers dismal prognosis and has limited treatment options. While immune-checkpoint inhibition (ICI) proved clinical efficacy in a variety of malignancies, data on the prognostic role of PD-L1 in MPE is scarce. We retrospectively studied PD-L1 tumour proportion score and Ki-67 index in pleural biopsies or cytologies from 123 patients (69 lung cancer, 25 mesothelioma, and 29 extrathoracic primary malignancies). Additionally, the impact of C-reactive protein (CRP) and platelet count was also analysed. Median overall survival (OS) after MPE diagnosis was 9 months. Patients with PD-L1 positive tumours (≥1%) had significantly shorter OS than patients with negative PD-L1 status (p = 0.031). CRP and Ki-67 index were also prognostic and remained independent prognosticators after multivariate analysis. Interestingly, Ki-67 index and CRP influenced the prognostic power of PD-L1. Finally, patients receiving ICI tended to have a longer median OS and CRP - but not PD-L1 - was a significant prognosticator in this subgroup. In summary, histological and circulating biomarkers should also be taken into account as potential biomarkers in ICI therapy and they may have an impact on the prognostic power of PD-L1. Our findings might help personalizing immune-checkpoint inhibition for patients with MPE and warrant further prospective validation.

Detection of ALK Gene Rearrangement in Cell-free RNA from Lung Cancer Malignant Pleural Effusion.

The aim of this study was to evaluate the feasibility of measuring ALK gene rearrangement in cell-free RNA (cf-RNA) of the supernatant from malignant pleural effusion (MPE). Supernatant, cell blocks, and matched sera samples were collected. Cf-RNA was isolated from the supernatant and sera, and cellular RNA was isolated from cell blocks. The ALK gene rearrangement in the cf-RNA was tested by the real-time polymerase chain reaction. Results showed that the concentration of cf-RNA was higher in the supernatant than in matched sera. ALK status concordance rates were 100% between the supernatant and cell blocks, while they were 0% between sera and cell blocks in ALK gene rearrangement cases. This suggests that using cf-RNA in MPE supernatant, but not in sera, could offer a reliable and robust surrogate strategy for the detection of ALK gene rearrangement.

Differential diagnosis of tuberculous and malignant pleural effusions: comparison of the Th1/Th2 cytokine panel, tumor marker panel and chemistry panel.

The differentiation between tuberculous plural effusion (TPE) and malignant plural effusion (MPE) remains a major clinical challenge in the diagnosis and management of pleural effusions, especially in developing countries with a high incidence of tuberculosis. We aimed to evaluate the diagnostic value of cytokines, tumor markers and biochemical markers in the differentiation of TPE and MPE. Two hundred and forty-two patients were included, of whom 134 were diagnosed with MPE and 108 were diagnosed with TPE. In total, 12 markers were tested in pleural effusion samples from all subjects: Interleukin-2 (IL-2), Tumor necrosis factor alpha (TNF-α), Interferon (IFN)-γ, interleukins-4, 6, 10 (IL-4,6,10), cytokeratin-19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE), adenosine deaminase (ADA), lactate dehydrogenase (LDH) and high sensitivity C- reactive protein (Hs-CRP). The diagnostic value of each marker was evaluated and compared by receiver operating characteristic (ROC) curves. In the 12 markers evaluated, TNF-α, IFN-γ, IL-6, CYFRA 21-1, CEA, ADA and Hs-CRP were significantly different between the TPE and MPE groups, and the areas under the ROC curves were 0.624, 0.942, 0.619, 0.808, 0.903, 0.842 and 0.917, respectively. IFN-γ showed a better diagnostic performance than the other markers. With a cut-off value of >2.45 pg/mL, the sensitivity and specificity of IFN-γ were 91.11 and 91.94%, respectively. TNF-α, IFN-γ, IL-6, CYFRA 21-1, CEA, ADA and Hs-CRP were useful in the differentiation between the TPE and MPE groups. IFN-γ showed a better diagnostic performance than the multitude of other markers evaluated in this study, which is satisfactory for the discrimination of TPE and MPE.

Analysis of tumor markers in pleural effusion and serum to verify the correlations between serum tumor markers and tumor size, TNM stage of lung adenocarcinoma.

BACKGROUND: The study of tumor markers (TM) in pleural effusion (PE) was not extensive. METHODS: TM in PE and serum were analyzed to determine whether TM was expressed in intrathoracic and extrathoracic tissues. To further verify the correlations between serum TM and tumor size, TNM stage of lung adenocarcinoma. RESULTS: Serum AFP was not correlated with tumor size, T stage, N stage, and M stage (P > .05). Serum CEA, serum CA125, serum CA15-3 were positively correlated with tumor size, T stage, N stage, M stage (P < .05). Serum CA19-9 was not significantly correlated with tumor size and T stage (P > .05), but was positively correlated with N stage and M stage (P < .05). The levels of PE CEA, PE CA125, PE CA15-3 were higher than those of serum CEA, serum CA125, serum CA15-3 (all P < .05). The level of PE AFP was lower than that of serum AFP (P < .05). The level of PE CA19-9 was not significantly different from that of serum CA19-9 (P > .05). The positive rates of PE CEA and PE CA125 were higher than those of serum CEA and serum CA125 (P < .05). The positive rates of PE AFP, PE CA15-3, PE CA19-9 were not significantly different from those of serum AFP, serum CA15-3, serum CA19-9 (P > .05).PE CEA, PE CA125, PE CA15-3 were moderately positively correlated with serum CEA, serum CA125, serum CA15-3, respectively (r = 0.597; r = 0.46; r = 0.583, all P < .05). However, PE AFP and PE CA19-9 were very strongly positively correlated with serum AFP and serum CA19-9, respectively (r = 0.888; r = 0.874, all P < .05). CONCLUSION: The expression characteristics of TM in PE and serum supported the correlations between serum TM and tumor size, TNM stage of lung adenocarcinoma.

Clinical value of haptoglobin and soluble CD163 testing for the differential diagnosis of tuberculous and malignant pleural effusions.

This study aims to evaluate the clinical value of haptoglobin (Hp) and sCD163 testing for the differential diagnosis of pleural effusion, and investigate the correlation of Hp and sCD163 with the inflammatory response of the body.Pleural effusion samples were collected from 78 patients (38 tuberculous pleural effusions [TPE] and 40 malignant pleural effusions [MPE]). The concentrations of Hp and sCD163 in the pleural effusion were measured by enzyme-linked immunosorbent assay (ELISA).The concentrations of Hp and sCD163 were significantly higher in the TPE group than in the MPE group (P < .05). The sensitivity and specificity of the Hp test for the differential diagnosis of TPE and MPE was 82.4% and 86.1%, respectively (P < .01), while the cut off value was 779.05 ug/mL. Furthermore, the sensitivity and specificity of the sCD163 test for the differential diagnosis of TPE and MPE was 76.3% and 85.0%, respectively (P < .01), while the cut off value was 16,401.11 ng/mL. Moreover, the sensitivity and specificity of the combination of Hp and sCD163 tests for diagnosing TPE was 90.0% and 87.5%, respectively. Hp and IL-1ß, TNF-α, CRP and ESR were positively correlated in both the TPE group and MPE group (P < .05). Hp and sCD163 were positively correlated in the TPE group (r = 0.3735, P = .0209), but not in the MPE group (r = 0.22, P = .1684). However, there was no correlation between sCD163 and TNF-α, CRP and ESR in either the TPE group, or the MPE group (P > .05). Furthermore, sCD163 and IL-1ß were weakly correlated in the TPE group (r = 0.49, P = .0018), but these had no correlation in the MPE group (r = 0.068, P = .6767).Hp and sCD163 can be used as biological markers for the differential diagnosis of pleural effusion in clinic, and the level of Hp in pleural effusion may reflect the intensity of inflammation in the body to some extent.

Comprehensive immune profiling and immune-monitoring using body fluid of patients with metastatic gastric cancer.

BACKGROUND: The aim of this study is to profile the cytokines and immune cells of body fluid from metastatic gastric cancer (mGC), and evaluate the potential role as a prognostic factor and the feasibility as a predictive biomarker or monitoring source for immune checkpoint inhibitor. METHODS: Body fluid including ascites and pleural fluid were obtained from 55 mGC patients and 24 matched blood. VEGF-A, IL-10, and TGF-ß1 were measured and immune cells were profiled by fluorescence assisted cell sorting (FACS). RESULTS: VEGF-A and IL-10 were significantly higher in body fluid than in plasma of mGC. Proportion of T lymphocytes with CD69 or PD-1, memory T cell marked with CD45RO, and number of Foxp3+ T regulatory cells (Tregs) were significantly higher in body fluid than those in blood of mGC. Proportion of CD8 T lymphocyte with memory marker (CD45RO) and activation marker (HLA-DR), CD3 T lymphocyte with PD-1, and number of FoxP3+ Tregs were identified as independent prognostic factors. When patients were classified by molecular subgroups of primary tumor, VEGF-A was significantly higher in genomically stable (GS)-like group than that in chromosomal instability (CIN)-like group while PD-L1 positive tumor cells (%) showed opposite results. Monitoring immune dynamics using body fluid was also feasible. Early activated T cell marked with CD25 was significantly increased in chemotherapy treated group. CONCLUSIONS: By analyzing cytokines and proportion of immune cells in body fluid, prognosis of patients with mGC can be predicted. Immune monitoring using body fluid may provide more effective treatment for patients with mGC.

High-throughput autoantibody analysis in malignant pleural effusion and tuberculosis pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) and tuberculosis pleural effusion (TPE) are 2 kinds of common pleural diseases. Finding efficient and accurate biomarkers to distinguish the 2 is of benefit to basic and clinical research. In the present study, we carried out the first high-throughput autoantibody chip to screen the beneficial biomarker with samples of MPE and TPE and the corresponding serum. METHODS: We collected pleural effusion and serum of patients with MPE (n = 10) and TPE (n = 10) who had been in Beijing Chao-Yang hospital from June 2013 to August 2014. Using RayBio Human Protein Array-G2 to measure the concentration of 487 defined autoantibodies. RESULTS: Fold changes of Bcl-2-like protein 11 (BIM) autoantibody in MPE-serum/TPE-serum and MPE/TPE groups were 10 (P = .019) and 6 (P = .001); for decorin autoantibody, MPE-serum/TPE-serum ratio was 0.6 (P = .029), and MPE/TPE ratio was 0.3 (P < .001). CONCLUSION: BIM autoantibody is a promising MPE biomarker by high-throughput autoantibody analysis in MPE and TPE.

PAI-1 Level Differences in Malignant Plural Effusion, Parapneumonic Pleuritis, and Cardiac Hydrothorax.

BACKGROUND AND OBJECTIVES: Plasminogen activator inhibitor-1 (PAI-1) is a fibrinolytic system enzyme whose role in various fibrinolytic processes is currently unknown. In clinical manifestations of pleural liquids of diverse etiology, various levels of fibrinolytic activity can be observed-parapneumonic processes tend to loculate in fibrin septa, while malignant pleural effusion (MPE) does not. The purpose of this study was to determine possible differences in PAI-1 levels in pleural effusions of varied etiology. MATERIAL AND METHODS: PAI-1 level in pleural effusion and serum was determined in 144 patients with pleural effusions of various etiology (cardiac hydrothorax-42 patients (29.2%), MPE-67 patients (46.5%), parapneumonic pleuritis-27 (18.8%), tuberculous pleuritis-6 patients (4.1%), pancreatogenic pleuritis-1 patient (0.7%) and pulmonary artery thromboembolism with pleuritis-1 patient (0.7%)). RESULTS: The median PAI-1 level (ng/mL) was the highest in the parapneumonic pleuritis group both in the effusion and the serum, with values of 291 (213-499) ng/mL and 204 (151-412) ng/mL, respectively, resulting in a statistically significant difference (p < 0.001) from the cardiac hydrothorax and MPE groups. However, there was no statistically significant difference between PAI-1 levels in the pleural effusion and serum in the cardiac hydrothorax and MPE groups. CONCLUSION: The PAI-1 level in MPE and cardiac hydrothorax was statistically significantly lower than in parapneumonic pleuritis.

Laboratory Discrimination Between Neutrophilic Malignant and Parapneumonic Pleural Effusions.

BACKGROUND: Malignant pleural effusion (MPE) occasionally demonstrates neutrophilic predominance, commonly found in parapneumonic pleural effusion (PPE). In comparison with lymphocytic MPE, neutrophilic MPE may have different characteristics associated with a more intense inflammatory response and poor prognosis. These characteristics of neutrophilic MPE may lead to inappropriate management and delayed diagnosis. Moreover, the limited diagnostic yield of microbiologic and cytologic tests makes early differential diagnosis between neutrophilic MPE and PPE more challenging. This study investigated objective laboratory findings to help distinguish neutrophilic MPE from PPE. MATERIALS AND METHODS: A retrospective study was conducted on patients with neutrophilic MPE and PPE. Routine blood and pleural fluid data of the 2 groups were compared, and the diagnostic performances of predictors for neutrophilic MPE were assessed using receiver-operating characteristic curves. RESULTS: Forty-one and 140 patients with neutrophilic MPE and PPE, respectively, were included. In final analysis, serum C-reactive protein, pleural fluid neutrophil-to-lymphocyte ratio, and pleural fluid carcinoembryonic antigen were significantly different between the 2 groups. With cut-off values of C-reactive protein <6.0 mg/dL, neutrophil-to-lymphocyte ratio <3.0 and carcinoembryonic antigen >8.0 ng/mL, the presence of any 2 or more parameters provided an area under the curve of 0.928 (95% CI, 0.851-0.999), yielding a sensitivity of 88%, specificity of 98%, positive predictive value of 92% and negative predictive value of 96% for identifying MPE. CONCLUSIONS: MPE should be considered even in patients with neutrophilic exudative effusion, especially if at least 1 predictor for neutrophilic MPE is present. Our results may help guide differentiation of neutrophilic MPE from PPE.