Pan-immune-inflammation and its dynamics: predictors of survival and immune-related adverse events in patients with advanced NSCLC receiving immunotherapy.

OBJECTIVES: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. PATIENTS AND METHODS: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3-4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. RESULTS: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3-4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). CONCLUSION: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.

PAFAH1B3 predicts poor prognosis and promotes progression in lung adenocarcinoma.

BACKGROUND: Recently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, its role in lung adenocarcinoma (LUAD) has not been reported until now. METHODS: The expression of PAFAH1B3 in LUAD was determined by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) analyses. A chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyze the prognostic value of PAFAH1B3. The CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and the cell cycle. The xenograft tumor model was constructed to explore the function of PAFAH1B3 in vivo. Western blot and IHC analyses were performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) and IHC analyses were used to analyze the effect of PAFAH1B3 on immune cell infiltration. RESULTS: Our study showed that the expression of PAFAH1B3 was upregulated in LUAD tissues and cells compared with noncancerous tissues and cells. Additionally, the results indicated that the expression of PAFAH1B3 was positively correlated with distant metastasis, TNM stage and poor clinical outcome and it was an independent prognostic risk factor for LUAD. In addition, silencing PAFAH1B3 suppressed cell proliferation, colony formation, and invasion and increased the cell population in the G0-G1 phases in vitro. Furthermore, our results showed that knockdown of PAFAH1B3 increased the epithelial marker E-cadherin level and decreased the mesenchymal marker N-cadherin level in vitro and in vivo. We also proved that PAFAH1B3 downregulation inhibited tumorigenesis and neutrophil infiltration in the xenograft tumor model. CONCLUSION: Our studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.

Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis.

BACKGROUND: Tumor cells display metabolic changes that correlate with malignancy, including an elevated hydrolysis of monoacylglycerol (MAG) in various cancer types. However, evidence is absent for the relationship between MAG lipolysis and NSCLC. METHODS: MAG hydrolase activity assay, migration, invasion, proliferation, lipids quantification, and transactivation assays were performed in vitro. Tumor xenograft studies and lung metastasis assays were examined in vivo. The correlations of MAGL/ABHD6 expression in cancerous tissues with the clinicopathological characteristics and survival of NSCLC patients were validated. FINDINGS: ABHD6 functions as the primary MAG lipase and an oncogene in NSCLC. MAG hydrolase activities were more than 11-fold higher in cancerous lung tissues than in paired non-cancerous tissues derived from NSCLC patients. ABHD6, instead of MAGL, was significantly associated with advanced tumor node metastasis (TNM) stage (HR, 1.382; P = 0.004) and had a negative impact on the overall survival of NSCLC patients (P = 0.001). ABHD6 silencing reduced migration and invasion of NSCLC cells in vitro as well as metastatic seeding and tumor growth in vivo. Conversely, ectopic overexpression of ABHD6 provoked the pathogenic potential. ABHD6 blockade significantly induced intracellular MAG accumulation which activated PPARα/γ signaling and inhibited cancer pathophysiology. INTERPRETATION: The present study provide evidence for a previously uncovered pro-oncogenic function of ABHD6 in NSCLC, with the outlined metabolic mechanisms shedding light on new potential strategies for anticancer therapy. FUND: This work was supported by the Project for Major New Drug Innovation and Development (2015ZX09501010 and 2018ZX09711001-002-003).

bFGF overexpression adipose derived mesenchymal stem cells improved the survival of pulmonary arterial endothelial cells via PI3k/Akt signaling pathway.

Pulmonary arterial hypertension (PAH) is characterized as pulmonary arterial endothelial dysfunction and endothelial cells over proliferation, therefore, the repair of pulmonary arterial endothelial cells has been a common goal in treating PAH. In the present study, human adipose derived mesenchymal stem cells (ASCs) were transfected with bFGF lentiviral vector and co-cultured with monocrotaline pyrrole treated human pulmonary arterial endothelial cells (HPAECs). The results showed that bFGF-ASCs improved the proliferation, viability and decreased the apoptosis of HPAECs, besides, improved PAH was observed in PAH rat models. Western blot analysis showed that the PI3k and p-Akt protein expression level increased in HPAECs, suggesting the activation of the PI3k/Akt signaling pathway. With the administration of LY294002, the bFGF induced HPAECs survival and PI3k/Akt signaling activation were successfully blocked. The present study demonstrated that bFGF transfected ASCs improved the survival of HPAECs by activating the PI3k/Akt pathway.

Function of Adipose-Derived Mesenchymal Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension through miR-191 via Regulation of BMPR2.

Pulmonary arterial hypertension (PAH) is a serious condition. However, prevailing therapeutic strategies are not effective enough to treat PAH. Therefore, finding an effective therapy is clearly warranted. Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear. Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs. Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs. In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved. Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation. And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group. Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats. Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2. These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.

Adipose-derived mesenchymal stromal cells improve hemodynamic function in pulmonary arterial hypertension: identification of microRNAs implicated in modulating endothelial function.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial endothelial hyperproliferation and dysfunction. Restoration of endothelial function is a common goal of available treatments. In the present study, human adipose-derived mesenchymal stromal cells (ASCs) were co-cultured with monocrotaline pyrrole-treated human pulmonary arterial endothelial cells (HPAECs); increased proliferation of HPAECs and expression of vascular endothelial growth factor (VEGF) were observed. High throughput sequencing results showed that six microRNAs (miMNAs) of ASCs were significantly dysregulated. In monocrotaline-induced PAH rat models, ASC transplantation improved the right ventricle systolic pressure, right ventricle hypertrophy and pulmonary endothelium hyperproliferation, and four of the six miRNAs were validated in the lung tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these dysregulated miRNAs were involved in the regulation of transcription, signal transduction, negative regulation of cell proliferation through mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, VEGF signaling pathway, cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, transforming growth factor (TGF)-beta signaling pathway and P53 signaling pathway. Our data indicates that the unique six miRNA expression signature could be involved in the PAH endothelial repair by ASCs.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a predictor of poor prognosis in non-small cell lung cancer, and its dynamic pattern following treatment with SGK1 inhibitor and γ-ray irradiation was elucidated.

The tumor suppressor gene p53 and its dynamic patterns have caused widespread attention in the field of cancer research. Serum and glucocorticoid-regulated kinase 1 (SGK1) with features of serine/threonine kinase activity, which also contributes to the structural and functional similarities with the AKT family of kinases, is a key enzyme in the regulation of immune responses in tumor cells, and SGK1 was noted to be expressed in close relation to p53 protein levels, and there exists a negative feedback pathway between intracellular SGK1 and p53. Noteworthy, SGK1 was detected to play a role in the development of resistance to cancer chemotherapy. In this study, we demonstrated that high SGK1 expression had strong prognostic value for reduced overall survival in NSCLC patients. Detection of SGK1 collectively was helpful to predict the prognosis of NSCLC. We also identified the expression level of SGK1 and the p53 pathway including downstream apoptotic proteins under the stimulation of γ-radiation and SGK1 inhibitor GSK650394, which presented a series of dynamic fluctuations. Our results suggest that SGK1 dynamics could play an important role in cell signaling, which is capable of directly influencing NSCLC cellular fate decisions.

Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload via regulating the crosstalk of Nrf2/ARE and TGF-ß/ smads pathways in rat heart.

Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor ß (TGF-ß) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-ß1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group. Rat models were established by incomplete constriction of abdominal aorta. After five weeks treatment, blood pressure, heart mass index (HMI), hemodynamic parameters and the average diameter of myocardium cell and collagen volume fraction (CVF) improved significantly in rosuvastatin groups, compared with the model group. Both rosuvastatin groups, increased in expression of Smad7, Nrf2, NAD (P) H dehydrogenase [quinone] 1 (Nqo1) and heme oxygenase 1(Ho1),and decreased in expression of TGF-ßl、Smad3 compared with the model group. Results from co-immunoprecipitation and GST pull down showed that Nrf2 interacts with Smad7. Our results revealed the crosstalk between TGF-ß1/Smads and Nrf2/ antioxidant response elements (ARE) pathways in myocardial remodeling through the interaction between Smad7 and Nrf2. Rosuvastatin can improve cardiac function and hypertrophy by regulating the crosstalk of the two signaling pathways.

CXCL6 promotes non-small cell lung cancer cell survival and metastasis via down-regulation of miR-515-5p.

Chemokine plays an important role in lung cancer and CXCL6 is one of chemokine, however, its effect on miRNAs profile and its roles in non-small cell lung cancer cell (NSCLC) is not elucidated. This study is purposed to explore the influence of CXCL6 on miRNA expression profile and found that CXCL6 could reduce the expression of miR-515-5p in NSCLC cells. MiR-515-5p in NSCLC cells could inhibit NSCLC survival and metastasis. MiR-515-5p acted as a tumor suppressor by targeting CXCL6 in NSCLC cells. These data highlighted a novel molecular interaction between miR-515-5p and CXCL6. MiR-515-5p may constitute a potential therapy target for NSCLC.

Effects of silencing Rab27a gene on biological characteristics and chemosensitivity of non-small cell lung cancer.

Rab27a, a member of the Rab protein family, can regulate the tumor microenvironment and promote the development of the tumor. Elevated expression of Rab27a is closely connected with many human cancers containing non-small cell lung cancer (NSCLC). But the role of Rab27a in non-small cell lung cancer and its possible mechanism is particularly unclear. In this research, we explored the effect of silencing Rab27a in vitro and in vivo, furnishing evidence that Rab27a could be a potential therapeutic target in NSCLC. Compared with corresponding control cells, silencing Rab27a had decreased ability of cell proliferation, migration and invasion in vitro and slower growth of xenograft tumors in mice. The expressions of apoptosis-associated proteins were induced with a reduction of anti-apoptotic protein in the NSCLC cells down-regulated Rab27a. Furthermore, Rab27a was associated with resistance to conventional chemotherapeutic agents. Our findings suggested that Rab27a might play a critical role in increasing chemosensitivity in NSCLC.

Panax notoginseng saponins reduce high-risk factors for thrombosis through peroxisome proliferator-activated receptor -γ pathway.

The classic Virchow theory suggests that blood stasis, hypercoagulability and endothelial dysfunction are three major factors that cause venous thrombosis (VT). It is a complicated biological process involved multi-factors. Platelet plays a central role and participates in multiple links of this process. Panax notoginseng saponins (PNS), the principal constituents derived from panax notoginseng, has been widely described for its anti-platelet activity. However, its potential mechanism against platelet aggregation has not been clarified. In this present study, we evaluated the anti-platelet effects of PNS on thrombin-induced platelet activation and its possible molecular mechanism of action, and further explored the therapeutic action of PNS on thrombin induced hypercoagulability in rat. Our results showed that PNS treatment inhibited platelet aggregation induced by thrombin, which was accompanied with over-expression of Peroxisome proliferator-activated receptor γ (PPAR-γ) protein, mRNA and upregulation of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) pathway in platelet, and this effect could be reversed by PPAR-γ inhibitor T0070907. In vivo, PNS significantly reversed thrombin-induced hypercoagulable state in rat which was accompanied by PPAR-γ protein and mRNA upregulation in rat lung. In conclusion, these data suggested that PNS could suppress thrombin-induced platelet aggregation in vitro and effectively improve hypercoagulable state in vivo and PNS-induced activation of PPAR-γ and its downstream PI3K/Akt/eNOS pathway played the central role.

Response of human non-small-cell lung cancer cells to the influence of Wogonin with SGK1 dynamics.

A number of significant studies in the field of cell biology have revealed another pattern of intracellular signal transduction in which cells transmit information through the dynamics of key signaling molecules. Dynamical properties of p53 have been demonstrated to be the key factor in dictating cell fate, including cell cycle arrest, permanent cell cycle arrest, and cell death. Previous studies showed a negative feedback regulation pathway between SGK1 and p53, but the dynamics of SGK1 have never been reported before. Therefore, we used different dosing strategies of Wogonin to affect SGK1 dynamics and investigate its impact on cell response. Key factors, such as APAF1, BAX, GADD45A, p21, PML, and YPEL3, which are related to cell cycle arrest, senescence, and apoptosis, were measured at different time points after incubation with Wogonin. Western blot and quantitative reverse transcriptase-polymerase chain reaction analysis were used to examine protein and mRNA expression of these genes. In addition, we also used ß-galactosidase staining and flow cytometric analysis to further verify the results. It was found that Wogonin inhibited cell viability and downregulated SGK1 protein levels; 20 µM Wogonin could induce non-small-cell lung cancer A549 cells into cell cycle arrest/senescence/apoptosis after 0.5/2/4 h, respectively; and SGK1 dynamics showed significant differences under different cell responses. Together, our findings showed that SGK1 protein dynamics can be an important part of intracellular signaling, directly influencing cellular response decisions.

Successful reduction of inflammatory responses and arachidonic acid-cyclooxygenase 2 pathway in human pulmonary artery endothelial cells by silencing adipocyte fatty acid-binding protein.

BACKGROUND: Adipocyte fatty acid-binding protein, also known as aP2 or fatty acid-binding protein 4 (FABP4), plays an important role in inflammatory and metabolic responses in adipocytes and macrophages. Recent work has demonstrated that macrophage FABP4 integrates inflammatory and lipid metabolic responses, thereby contributing to the development of insulin resistance and atherosclerosis. However, it is not known whether FABP4 in human pulmonary artery endothelial cells(HPAECs) modulates inflammation. RESULTS: Here, we demonstrate that FABP4 and inflammatory cytokines are upregulated in lipopolysaccharide(LPS)-stimulated HPAECs. In addition, LPS increases the expression of molecules in the arachidonic acid(AA)-cyclooxygenase (COX) 2 signaling pathway in FABP4-expressing, but not FABP4-deficient, HPAECs. CONCLUSIONS: Our findings demonstrate that silencing FABP4 could decrease inflammatory cytokines, which were reported to be expressed via the AA-COX2 pathway, in HPAECs. In addition, silencing FABP4 could inhibit the expression of molecules in the AA-COX2 pathways. So we speculate silencing FABP4 could decrease the inflammatory response in HPAECs, which involves in the AA-COX2 signaling pathway. Our study suggests that FABP4 could be a potential biomarker and intervention point for the inflammation-related disease in HPAECs such as pulmonary thromboembolism.

Red cell distribution width in predicting 30-day mortality in patients with pulmonary embolism.

PURPOSE: The aim of the study was to investigate red cell distribution width (RDW) in predicting 30-day mortality in patients with pulmonary embolism (PE). METHODS: A single-center, retrospective study design was used between January 1, 2014, and February 1, 2016. The primary end point was 30-day mortality after admission. The RDW predicting value was assessed by receiver operating characteristic curves and area under the curve. RESULTS: A total of 309 patients with PE were included. The 30-day mortality was 14.9% (46/309). The mean RDW level was 13.9%±0.6% (range, 10.7%-21.9%) at admission. The 30-day mortality was higher in the high-RDW-level group compared with the normal-RDW-level group (12.5% vs 23.5%, χ2=5.140, P=.023), with an odds ratio of 2.164 (95% confidence interval [CI], 1.019-4.450). Logistic regression showed that presence of shock, RDW level, and simplified pulmonary embolism severity index (sPESI) were independent risk factors for 30-day mortality in patients with PE. After adjustment by these risk factors, the adjusted odds ratio was 1.439 (95% CI, 1.024-2.116). The area under the curve for RDW predicting the 30-day mortality was 0.6646 (95% CI, 0.5585-0.7518). The cutoff was 16%. The Youden index for RDW and sPESI was 0.400 and 0.453, respectively. When adding RDW into sPESI, the modified sPESI showed highest prediction accuracy, with Youden index 0.499. CONCLUSIONS: Our results suggested that the RDW is a simple and useful indicator in predicting 30-day mortality in patients with PE. However, this conclusion showed be confirmed by prospective study with large sample.

Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (NSCLC).

Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT). The epithelial markers E-cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis-associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA-IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non-cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5-year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.

Hyponatremia and short-term prognosis of patients with acute pulmonary embolism: A meta-analysis.

OBJECTIVES: The aim of this study was to assess the relationship between hyponatremia and the short-term prognosis of patients with acute pulmonary embolism (PE). METHODS: Searches of MEDLINE (1966-) and ISI Databases (1965-) were performed for English language studies. Odds ratio (OR) and adjusted hazard ratio (HR) for short-term prognosis were calculated for PE patients with or without hyponatremia. Meta-analysis was carried out following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. RESULTS: Eight studies with 18,616 patients were included in this meta-analysis. The mean in-hospital mortality was 12.9% in hyponatremia group, compared with 2.3% in normonatremia group. Meta-analysis showed the summary OR was 5.586 (95% CI 3.424 to 9.112). The mean 30-day mortality was 15.9% in hyponatremia group, compared with 7.4% in normonatremia group. The summary OR was 3.091 (95% CI 1.650 to 5.788). No significant publication bias was found for the meta-analysis. Sensitivity analyses by only pooled the adjusted HRs showed the summary HR was 0.924 (95% CI 0.897 to 0.951), which indicted the mortality risk will be decrease to 0.924 times for per-1mmol/L sodium increase in hyponatremia patients. CONCLUSIONS: Our meta-analysis indicates that hyponatremia was related with poor short-term prognosis in patients with acute PE. Hyponatremia is a simple, cheap, powerful marker of mortality, which should be used routinely tested in the PE prognostic assessment.

Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism.

Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.

Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC).

Fatty acid binding proteins (FABPs) are intracellular lipid-binding proteins that are involved in a variety of biological cellular processes, including tumorigenesis. In this study, we explored the expression pattern of FABP3 and FABP4 in non-small cell lung cancer (NSCLC) as well as their roles in prognosis. We determined mRNA expression of FABP3 and FABP4 in matched pairs of cancerous and non-cancerous fresh frozen tissues from 30 NSCLC patients. Tissue microarray immunohistochemical analysis (TMA-IHC) was applied to determine the protein expression of FABP3 and FABP4 in 281 cancerous and 121 matched adjacent non-cancerous tissue samples. Our results showed that both mRNA and protein expression of FABP3 and FABP4 were significantly higher in cancerous tissues when compared to non-cancerous tissues. Furthermore, high expression of FABP3 or FABP4 in NSCLC was significantly associated with advanced tumor node metastasis (TNM) stage and had a negative impact on the overall survival of NSCLC patients. Concurrent high expression of FABP3 and FABP4 was significantly related to TNM stage. In conclusion, our research demonstrated that high FABP3 or FABP4 expression had strong prognostic value for overall survival in NSCLC. Detection of FABP3 and FABP4 cooperatively was helpful to predict the prognosis of NSCLC.

Pollutional haze and COPD: etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.

In recent years, serious pollutional haze occurs in the mainland of China thanks to the development of urbanization and industrialization. There is a close relationship between air pollution and the occurrence and development of chronic obstructive pulmonary disease (COPD), but there are some new characteristics in some aspects of COPD associated with pollutional haze compared with COPD induced by traditional physical and chemical factors. This article attempts to summarize the new progress from these new features of COPD related to pollutional haze, focus on etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.