Effect of glioma-derived immunoglobulin on biological function of glioma cells.

INTRODUCTION: Glioma is the most common and most invasive primary central nervous system tumour, and it is urgent to develop new specific therapeutic targets. Studies have confirmed that epithelial-derived tumour cells promote tumour cell proliferation and metastasis by secreting a large number of immunoglobulins (Igs), but the role of tumour-derived Igs in glioma has never been reported. METHODS: The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyse the Ig transcription and its correlation with the prognosis of patients with glioma. Immunohistochemistry and immunofluorescence were used to detect the protein expression of IgG and IgM in the glioma tissues of patients and glioma cell lines. When IgG was knocked down by small interfering RNA or knocked out by CRISPR-Cas9, the function of proliferation and migration of glioma cells were analysed by CCK-8, clone formation, wound healing, and transwell assays. Changes in proteins and their phosphorylation in signalling pathways were detected by western blotting. The nude mouse subcutaneous tumour-bearing model was established to analyse the effect of IgG in vivo. RESULTS: The transcriptional level of IgG was pretty high in glioma tissues and was positively correlated with high WHO grade, recurrence, and poor prognosis. The expression of IgG and IgM was found in tumour tissues and human glioma cell lines U87 and U251, and the main expression form was secreted. Decreased IgG inhibited the proliferation and migration of glioma cells. Knockout or knockdown of IgG downregulated the phosphorylation of the key molecules in the MAPK and PI3K/Akt pathway through the HGF/SF-Met or FAK/Src pathway. In vivo tumourigenesis mouse model confirmed that reduced IgG expression inhibited glioma growth. CONCLUSION: Ig was expressed in glioma tissues and cell lines, and a high expression level predicted a poor prognosis of patients. Glioma-derived IgG promoted glioma cell proliferation and migration through the HGF/SF-Met or FAK/Src pathway.

Elevations of monocyte and neutrophils, and higher levels of granulocyte colony-stimulating factor in peripheral blood in lung cancer patients.

INTRODUCTION: Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. METHODS: One hundred and thirteen patients with lung cancer and 99 age-matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony-stimulating factors were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction in antitumor NK cells (p < 0.0001) and an increase in the protumor MDSCs (p < 0.0001) were observed in the lung cancer patients compared with the controls. Monocyte counts were significantly higher in lung cancer patients with histories of smoking (p < 0.05) or drinking (p < 0.01) than in patients with no relevant history or healthy controls. The number of neutrophils and the neutrophil-to-lymphocyte ratio (NLR) were particularly higher in patients with liver metastasis (p < 0.01) compared with no metastasis patients or healthy controls. Levels of the monocyte-derived cytokine interleukin-6 (p < 0.05), granulocyte colony-stimulating factor (G-CSF) (p < 0.0001), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.0001) were higher in patients than in controls. G-CSF levels decreased during the remission phase (p < 0.05), and positively correlated with carbohydrate antigen 19-9 (p < 0.05) and gene mutation (p < 0.05). CONCLUSION: Monocyte and neutrophil counts were higher in peripheral blood in lung cancer patients than in controls, especially when patients had histories of smoking, drinking, and liver metastasis. Serum levels of G-CSF and GM-CSF were higher in lung cancer patients, and G-CSF levels positively correlated with disease severity.

Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis.

Background: Pigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy. Method: In this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14+ cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function. Results: The most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA. Conclusion: The transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.