scholarly journals Caspase Recruitment Domain Containing Protein 9 Suppresses Non-Small Cell Lung Cancer Proliferation and Invasion via Inhibiting MAPK/p38 Pathway

2020 ◽  
Vol 52 (3) ◽  
pp. 867-885
Author(s):  
Linyue Pan ◽  
Yuting Tan ◽  
Bin Wang ◽  
Wenjia Qiu ◽  
Yulei Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
B Cell Lymphoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects ◽  
Nsclc Patients ◽  
P38 Pathway

PurposeCaspase recruitment domain containing protein 9 (CARD9) has been demonstrated to be a pro-tumor factor in various cancers. However, our previous study found a significant decrease of CARD9 in malignant pleural effusion compared with benign pleural effusion. So we investigated the role of CARD9 in non-small cell lung cancer (NSCLC) and its working mechanism. Materials and MethodsImmunohistochemistry, western blot, and quantitative real-time polymerase chain reaction were used to detect the expression of CARD9 in specimens of NSCLC patients. The Cancer Genome Atlas (TCGA) databasewas also used to analyze the expression of CARD9 in NSCLC and its predicting value for prognosis. Immunofluorescence was used for CARD9 cellular location. Cell growth assay, clonal formation assay, wound healing assay, matrigel invasion assay, and flow cytometry were used to test cell proliferation, migration, invasion, apoptosis, and cycle progression of NSCLC cells with CARD9 knockdown or CARD9 overexpression. Co-immunoprecipitation was used to identify the interaction between CARD9 and B-cell lymphoma 10 (BCL10). SB203580 was used to inhibit p38 activation.ResultsCARD9 was decreased in NSCLC tissues compared with normal tissues; low CARD9 expression was associated with poor survival. CARD9 was expressed both in tumor cells and macrophages. Downregulation of CARD9 in NSCLC cells enhanced the abilities of proliferation, invasion and migration via activated MAPK/p38 signaling, while overexpression of CARD9 presented antitumor effects. BCL10 was identified to interact with CARD9.ConclusionWe demonstrate that CARD9 is an independent prognostic factor in NSCLC patients and inhibits proliferation, migration, and invasion by suppressing MAPK/p38 pathway in NSCLC cells.

scholarly journals The Prognostic Value of LDH And ADA in Serum and Pleural Fluid of Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Shuang Zhao ◽  
Jun Zeng ◽  
Juanli Wu
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Pleural Fluid ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnosis Method ◽  
Nsclc Patients ◽  
Worse Prognosis

Abstract Objective: To explore the value of dehydrogenase (LDH) and adenosine deaminase (ADA) in serum and pleural fluid in predicting the prognosis of non-small cell lung cancer.Methods: A total of 134 patients with non-small cell lung cancer (NSCLC) with pleural effusion were enrolled. LDH in Serum and LDH and ADA in pleural fluid were detected, and the cancer ratio (serum LDH/pleural fluid ADA ratio) was calculated. Patients were followed until death. To analyze the correlation between the above indicators and the clinical pathological characteristics of the patients, and the predictive value for the prognosis of the patients.Results: Among the included NSCLC patients with pleural effusion, the average age was 61.76 years old, mainly male (66.7%), the right lung was more common (47.2%), adenocarcinoma was the main (82.1%), and smoking patients accounted for 48.0%. In the diagnosis method, there were 94 cases were diagnosed by pleural fluid exfoliated cells or pleural biopsy. In terms of clinical features, serum LDH is only related to adrenal metastasis (p = 0.000), and pleural fluid LDH is related to the patient's pathological type (p = 0.001). There was no correlation between pleural fluid ADA or cancer ratio and patient gender, lesion location, pathological type, diagnosis method, smoking history, and metastatic location. In terms of prognostic value, patients with ADA < 20U/L and cancer ratio >20 have shorter overall survival and worse prognosis (​​p < 0.0001 and p = 0.0178, respectively). The multivariate Cox regression analysis suggested that the cancer ratio (HR = 1.699, 95%CI: 1.097–2.630, p = 0.017) was an independent risk factor for the poor prognosis of patients.Conclusion: The NSCLC patients with pleural fluid ADA < 20U/L and cancer ratio > 20 combined with pleural effusion had a shorter overall survival and worse prognosis.

Up-regulated HMGB1 in the pleural effusion of non-small cell lung cancer (NSCLC) patients reduces the chemosensitivity of NSCLC cells

2018 ◽  
Vol 104 (5) ◽  
pp. 338-343 ◽  
Author(s):  
Ying Ma ◽  
Shirong Kang ◽  
Xu Wu ◽  
Bateer Han ◽  
Zhiyong Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Background: Pleural effusion is one of the complications of human non-small cell lung cancer (NSCLC). High mobility group box-1 protein (HMGB1) correlates highly with invasion and metastasis in multiple tumors. The aim of this study was to explore the clinical value of HMGB1 in NSCLC patients, and to investigate the role of HMGB1 in the development of pleural effusion. In addition, we also investigated the regulatory role of HMGB1 in the sensitivity of NSCLC cells to cisplatin. Methods: 46 NSCLC malignant pleural effusion (MPE) and 31 benign pleural effusion samples were quantitatively analyzed with Enzyme-Linked Immunosorbent Assay (ELISA) for cytokines, such as IL-1beta, IL-6, IL-8 and HMGB1. The HMGB1 expression in NSCLC tissues was examined with RT-qPCR and western blotting methods. Then the influence by HMGB1 on the chemosensitivity of lung cancer A549 cells was examined with MTT assay and colony forming assay for the A549 cells post the treatment with cisplatin or (and) HMGB1. Results: The results demonstrated that HMGB1 was up-regulated in the pleural effusion of NSCLC patients, along with the up-regulated levels of proinflammatory cytokines such as IL-6 and IL-8. And the up-regulation of HMGB1 was confirmed at both the mRNA and protein levels in the NSCLC tissues. Recombinant HMGB1 reduced the sensitivity of A549 cells to cisplatin in vitro. Conclusions: In conclusion, HMGB1 was up-regulated in the pleural effusion and tumor tissues of NSCLC patients. HMGB1 reduced the sensitivity of NSCLC A549 cells to cisplatin in vitro.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1794
Author(s):  
Alice Indini ◽  
Erika Rijavec ◽  
Francesco Grossi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Circulating Biomarkers ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

scholarly journals 1318P Association between soluble PD-L1 and prognosis of non-small cell lung cancer (NSCLC) patients treated with immunotherapy

2020 ◽  
Vol 31 ◽  
pp. S851
Author(s):  
C. Dellepiane ◽  
S. Coco ◽  
M.G. Dal Bello ◽  
G. Rossi ◽  
E. Rijavec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients
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