Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation.

Background: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. Methods: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. Results: WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. Conclusion: IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC.

The Highly Expressed IFIT1 in Nasopharyngeal Carcinoma Enhances Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells.

In this study, we aimed to identify potential targets modulating the progression of nasopharyngeal carcinoma (NPC) using integrated bioinformatics analysis and functional assays. Differentially expressed genes (DEGs) between NPC and normal tissues samples were obtained from publicly availably microarray datasets (GSE68799, GSE34573, and GSE53819) in the Gene Expression Omnibus (GEO) database. The bioinformatics analysis identified 49 common DEGs from three GEO datasets, which were mainly enriched in cytokine/chemokine pathways and extracellular matrix organization pathway. Further protein-protein interaction network analysis identified 11 hub genes from the 49 DEGs. The 11 hub genes were significantly up-regulated in the NPC tissues when compared to normal tissues by analyzing the Oncomine database. The 8 hub genes including COL5A1, COL7A1, COL22A1, CXCL11, IFI44L, IFIT1, RSAD2, and USP18 were significantly up-regulated in the NPC tissues when compared to normal tissues by using the Oncomine database. Further validation studies showed that IFIT1 was up-regulated in the NPC cells. Knockdown of IFI1T1 suppressed the proliferation, migration, and invasion of NPC cells; while IFIT1 overexpression promoted the proliferation, migration, and invasion of NPC cells. In conclusion, a total of 49 DEGs and 11 hub genes in NPC using the integrated bioinformatics analysis. IFIT1 was up-regulated in the NPC cells lines, and IFIT1 may act as an oncogene by promoting NPC cell proliferation, migration, and invasion.

CXCR1 correlates to poor outcomes of EGFR-TKI against advanced non-small cell lung cancer by activating chemokine and JAK/STAT pathway.

OBJECTIVE: CXCR1, a member of the seven-transmembrane chemokine receptor family, promotes cell proliferation and metastasis in many tumors. The present study was undertaken to explore the interrelation between CXCR1 expression and the prognosis of advanced non-small cell lung cancer (NSCLC) in addition to the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (LUAD). METHODS: The expression of CXCR1 in NSCLC tissues was assessed by immunohistochemistry. The relationships between CXCR1 expression and clinical-pathological factors were investigated. Concomitantly, the relationship between CXCR1 expression and EGFR-TKI treatment efficacy was investigated. Gene set enrichment analysis (GSEA) was employed for the exploration of pathway enrichment, tumor immune estimation resource (TIMER) and gene expression profiling interactive analysis (GEPIA) for the inspection of the interrelationship between infiltration immune cells and CXCR1. After gain-and loss-of-function of CXCR1 in NSCLC cells, qRT-PCR and Western blot were applied to measure the levels of proteins associated with the chemokine pathway (CCL3 and CXCL2) and the JAK/STAT pathway (IL9R, PIAS4 and STAT5A). RESULTS: CXCR1 significantly correlated with poor prognosis of NSCLC patients. Additionally, CXCR1 limited the clinical efficacy of EGFR-TKIs in advanced LUAD (P = 0.029). In the tumor microenvironment, CXCR1 was positively associated with infiltration levels of immune markers in lung squamous cell carcinoma (LUSC) and LUAD. High expression of CXCR1 was implicated in the NOD-like receptor (NLR), cytokine/cytokine receptor, JAK/STAT and chemokine signaling pathways in LUAD and LUSC. Overexpression of CXCR1 in NSCLC cell lines enhanced expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A, while knockdown of CXCR1 repressed expressions of CCL3, CXCL2, IL9R, PIAS4 and STAT5A. CONCLUSION: CXCR1 is correlated with poor prognosis of NSCLC and affects the efficacy of EGFR-TKIs in LUAD.

FAM83A drives PD-L1 expression via ERK signaling and FAM83A/PD-L1 co-expression correlates with poor prognosis in lung adenocarcinoma.

PURPOSE: The purpose of this research was to explore the correlation and prognostic significance of FAM83A and programmed cell death-ligand 1 (PD-L1) protein expression in patients with lung adenocarcinoma (LUAD). METHODS: A total of 130 LUAD specimens and 50 normal lung tissue specimens were analyzed for both FAM83A and PD-L1 expression by immunohistochemistry (IHC) analysis. The effect of FAM83A on PD-L1 and ERK pathway was evaluated by RT-PCR and western blot in vitro. RESULTS: Both FAM83A and PD-L1 were upregulated in patients with LUAD and co-expression of them was significantly associated with tumor stage, metastasis and worse survival in LUAD. Multivariate cox regression analysis revealed that co-expression of FAM83A and PD-L1 was an independent prognostic factor impacting survival. Moreover, experiments in vitro showed FAM83A could promote the expression of PD-L1 through the ERK pathway. CONCLUSION: FAM83A and PD-L1 may be potential therapeutic targets for LUAD. Co-expression of FAM83A and PD-L1 in tumor cells was a credible biomarker predictor for worse survival in resected cases. FAM83A may promote the expression of PD-L1 through ERK signaling pathway, thus causing immune escape of tumor.

TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer.

Nonsmall cell lung carcinoma (NSCLC) contributes to the highest number of cancer deaths globally. Metastases and chemoresistance are two major confounders to the treatment efficacy in NSCLC. Transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) has been associated with high rates of metastases in breast, gastric, and stomach cancers. However, the role of TBL1XR1 in lung cancers remains underexplored. We selected matched and cancerous lung tissues to establish the upregulation of TBL1XR1. Using in vitro assays, we assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model (A549 cells), and H460 cell lines overexpressing TBL1XR1. We found that TBL1XR1 is overexpressed in NSCLC tissue and patient sera in comparison to paired adjacent normal tissue. Overexpression of TBL1XR1 in NSCLC cell lines mediates cell survival, proliferation, and metastases. TBL1XR1 was found to regulate MEK and Akt pathways through their master regulator c-Met. We observed that activation of c-Met is downregulated in the absence of TBL1XR1. Our study strengthens the contention that TBL1XR1 is a biomarker for prognosis of NSCLC. It may also be considered as an adjunct or core therapeutic target to overcome cisplatin resistance in lung cancers.

FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.

Family with sequence similarity 83, member A (FAM83A), as a potential tumor promoter, was reported to contribute to the progression of several malignant tumors. However, the significance of FAM83A in invasion and metastasis of non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that FAM83A expression was significantly increased in NSCLC tissues. High expression of FAM83A was positively associated with tumor metastasis and poor survival of NSCLC patients. Functional experiments revealed that FAM83A knockdown could suppress NSCLC cell migration and invasion both in vivo and in vitro. While opposite results were observed in FAM83A-transfected cells. Mechanically, we found that FAM83A promoted NSCLC cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) via PI3K/ATK/Snail signaling. Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis. Taken together, our findings are the first time to demonstrate that increased expression of FAM83A in NSCLC was correlated with EMT and tumor metastasis, which may provide a novel therapeutic target in NSCLC treatment.

Multidimensional Ternary Hybrids with Synergistically Enhanced Electrical Performance for Conductive Nanocomposites and Prosthetic Electronic Skin.

Graphene and silver nanowires (AgNWs) are ideal fillers for conductive polymer composites, but they tend to aggregate in the polymer matrix due to the lack of surface functional groups and large specific surface area, which is hard for the polymer composites filled with them to reach their full potential. Here, ternary hybrids with multidimensional architectures including 3D polystyrene (PS) microspheres, 2D reduced graphene oxide (RGO) nanosheets, and 1D AgNWs are obtained using a simple, but effective, electrostatic attraction strategy. The electrical conductivity (136.25 S m-1) of the ternary hybrid conductive nanocomposites filled with RGO and AgNWs is significantly higher than that of the nanocomposites containing only RGO (3.255 S m-1) at the same total filler loading due to the synergistic effect of RGO and AgNWs. The conductive nanocomposites simultaneously present a low percolation threshold of 0.159 vol % and a maximum electrical conductivity of 1230 S m-1 at 3.226 vol % filler loading. Moreover, a flexible electronic skin based on the multidimensional ternary hybrids is presented, and it exhibits large stretchability, high gauge factor, and excellent cyclic working durability, which is successfully demonstrated in monitoring prosthetic finger motions.

The value of prognostic factors in Chinese patients with small cell lung cancer: A retrospective study of 999 patients.

INTRODUCTION: Little is known about the prognostic factors for small cell lung cancer (SCLC) in Chinese patients. OBJECTIVE: The aim of this retrospective study was to improve our understanding of overall survival (OS) and progression-free survival (PFS) prognostic factors in Chinese patients with SCLC. METHODS: A retrospective analysis of 999 SCLC cases was performed. Patient characteristics, treatments, and laboratory data, including platelet counts and serum lactate dehydrogenase (LDH) and serum sodium levels, were collected. Potential prognostic factors for OS and PFS were evaluated by univariate and multivariate analyses. RESULTS: The median OS and PFS were 10.6 and 7.0 months, respectively. The multivariate Cox proportional hazards model was used to identify stage, serum LDH, and several therapy-relevant factors, including the initial chemotherapy regimen, number of initial chemotherapy cycles, and combination therapy, as independent prognostic factors for OS. Furthermore, female sex, normal LDH levels, a response to therapy, receiving six cycles of initial chemotherapy, and receiving chemotherapy combined with radiotherapy and/or surgery were favorable prognostic factors for PFS. In addition, patients with hyponatremia had a worse OS; therefore, hyponatremia could not influence survival when a good response to therapy was achieved, and it failed to predict PFS. CONCLUSIONS: This study demonstrated that several factors, including patient, tumor, and treatment characteristics and serum LDH levels are independent prognostic factors for OS and PFS in Chinese patients with SCLC. The identification of such factors will help physicians compare different populations and to interpret the contribution of treatment to differences in survival among groups.

Facet-Dependent Property of Sequentially Deposited Perovskite Thin Films: Chemical Origin and Self-Annihilation.

Quantification of intergrain length scale properties of CH3NH3PbI3 (MAPbI3) can provide further understanding of material physics, leading to improved device performance. In this work, we noticed that two typical types of facets appear in sequential deposited perovskite (SDP) films: smooth and steplike morphologies. By mapping the surface potential as well as the photoluminescence (PL) peak position, we revealed the heterogeneity of SDP thin films that smooth facets are almost intrinsic with a PL peak at 775 nm, while the steplike facets are p-type-doped with 5-nm blue-shifted PL peak. Considering the reaction process, we propose that the smooth facets have well-defined crystal lattices that resulted from the interfacial reaction between MAI and PbI2 domains containing low trap states density. The steplike facets are MAI-rich originated from the grain boundaries of PbI2 film and own more trap states. Conversion of steplike facets to smooth facets can be controlled by increasing the reaction time through Ostwald ripening. The improved stability, photoresponsivity up to 0.3 A/W, on/off ratio up to 3900, and decreased photo response time to ∼160 µs show that the trap states can be annihilated effectively to improve the photoelectrical conversion with prolonged reaction time and elimination of steplike facets. Our findings demonstrate the relationship between the facet heterogeneity of SDP films and crystal growth process for the first time, and imply that the systematic control of crystal grain modification will enable amelioration of crystallinity for more-efficient perovskite photoelectrical applications.

Flexible Asymmetrical Solid-State Supercapacitors Based on Laboratory Filter Paper.

In this study, a flexible asymmetrical all-solid-state supercapacitor with high electrochemical performance was fabricated with Ni/MnO2-filter paper (FP) as the positive electrode and Ni/active carbon (AC)-filter paper as negative electrode, separated with poly(vinyl alcohol) (PVA)-Na2SO4 electrolyte. A simple procedure, such as electroless plating, was introduced to prepare the Ni/MnO2-FP electrode on the conventional laboratory FP, combined with the subsequent step of electrodeposition. Electrochemical results show that the as-prepared electrodes display outstanding areal specific capacitance (1900 mF/cm(2) at 5 mV/s) and excellent cycling performance (85.1% retention after 1000 cycles at 20 mA/cm(2)). Such a flexible supercapacitor assembled asymmetrically in the solid state exhibits a large volume energy density (0.78 mWh/cm(3)) and superior flexibility under different bending conditions. It has been demonstrated that the supercapacitors could be used as a power source to drive a 3 V light-emitting diode indicator. This study may provide an available method for designing and fabricating flexible supercapacitors with high performance in the application of wearable and portable electronics based on easily available materials.

Copper salts mediated morphological transformation of Cu2O from cubes to hierarchical flower-like or microspheres and their supercapacitors performances.

Monodisperse Cu2O of different microstructures, such as cubes, flower-like, and microspheres, have been extensively synthesized by a simple polyol reduction method using different copper salts, i.e. (Cu(acac)2, Cu(OH)2, and Cu(Ac)2·H2O). The effects of copper salts on the morphology of Cu2O were investigated in details through various characterization methods, including X-ray diffraction, transmission electron microscopy, scanning electron microscopy and UV-Vis absorption spectra. The effects of morphology on the electrochemical properties were further studied. Among the different structures, Cu2O with the microspheric morphology shows the highest specific capacitance and the best cycling stability compared with those of the other two structures, thus bear larger volume charge during the electrochemical reaction due to the microspheres of small nanoparticles.