Dataset Information

[Correlation between the Expression of PD-L1 in Pleural Effusion of Lung Adenocarcinoma and the Clinicopathological Features and Molecular Changes].

ABSTRACT: BACKGROUND:Pembrolizumab, an immunotherapy for advanced non-small cell lung cancer (NSCLC), needs to predict treatment response based on test results including immunohistochemistry (IHC), which detects the expression of programmed death ligand 1 (PD-L1). The aim of this study was to evaluate the feasibility of immunocytochemistry (ICC) in NSCLC cytology to detect PD-L1 and to investigate the correlation between PD-L1 expression and clinical pathology and molecular features. METHODS:Sixty cases of lung adenocarcinoma pleural cytology were collected and PD-L1 sp263 reagent was used for immunocytochemical staining according to the manufacturer's instructions. Next-generation sequencing (NGS) was performed on pleural cytology specimens to explore its correlation. RESULTS:Of the 60 cases of lung adenocarcinoma pleural effusion cell block, 35 cases were positive for PD-L1 expression, and the positive expression rate was 58.3%. The positive rate of PD-L1 expression in the specimens of our hospital was 33.3%, and there was no significant difference between the cytological specimens and the histological specimens (P>0.05). Of the 60 cytological specimens, 26 were tested for NGS, and 15 (57.7%) were found to have epidermal growth factor receptor (EGFR) mutations. No correlation was found between PD-L1 expression and EGFR mutation. The positive expression rate of PD-L1 were not correlated with the age and gender in the study population (P>0.05). CONCLUSIONS:When no surgical specimens are available, pleural cytology cell block specimens can be used for immunocytochemical detection of PD-L1, and the results are feasible.

SUBMITTER: Ma H

PROVIDER: S-EPMC7118327 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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[Correlation between the Expression of PD-L1 in Pleural Effusion of Lung Adenocarcinoma and the Clinicopathological Features and Molecular Changes].

Ma Haiyue H Jia Jia J Guo Huiqin H Zhao Huan H Wang Cong C Zhao Linlin L Sun Yue Y Li Weihua W Zhang Zhihui Z

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20200301 3

<h4>Background</h4>Pembrolizumab, an immunotherapy for advanced non-small cell lung cancer (NSCLC), needs to predict treatment response based on test results including immunohistochemistry (IHC), which detects the expression of programmed death ligand 1 (PD-L1). The aim of this study was to evaluate the feasibility of immunocytochemistry (ICC) in NSCLC cytology to detect PD-L1 and to investigate the correlation between PD-L1 expression and clinical pathology and molecular features.<h4>Methods</h ...[more]

PMID: 32209183

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Project description:Background: Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear. Aim: The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies. Patients and Methods: Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion. Results: 50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46-100%), 63% (36-84%), 45% (18-75%) and 100% (66-100%), and with expression ≥1% defined as positive 86% (56-97%), 43% (12-80%), 75% (47-92%) and 60% (17-93%). Conclusion: PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281).

Project description:BackgroundPleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer.MethodsThe exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion.ResultsWe identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD via the exosomal hsa-miR-3120-5p-PRF1 axis.ConclusionsWe identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE.

Dataset Information

[Correlation between the Expression of PD-L1 in Pleural Effusion of Lung Adenocarcinoma and the Clinicopathological Features and Molecular Changes].

Publications

[Correlation between the Expression of PD-L1 in Pleural Effusion of Lung Adenocarcinoma and the Clinicopathological Features and Molecular Changes].

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