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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
Published on: October 26, 2017
Exploring effective biomarkers and potential immune related gene in small cell lung cancer
Yang Yunchu1, Akihiko Miyanaga2, Kuniko Matsuda1
1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Abstract:
Small cell lung cancer (SCLC) is well known as a highly malignant neuroendocrine tumor. Immunotherapy combined with chemotherapy has become a standard treatment for extensive SCLC. However, since most patients quickly develop resistance and relapse, finding new therapeutic targets for SCLC is important. We obtained four microarray datasets from the Gene Expression Omnibus database and screened differentially expressed genes by two methods: batch correction and "RobustRankAggregation". After the establishment of a protein-protein interaction network through Cytoscape, seven hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA) with high expression in SCLC samples were obtained by eight CytoHubba algorithms. The Least Absolute Shrinkage and Selection Operator regression and the Wilcoxon test were used to analyze the differences in the immune cells' infiltration between normal and SCLC samples. The contents of seven kinds of immune cells were considered to differ significantly between SCLC samples and normal samples. A negative association was found between BIRC5 and monocytes in the correlation analysis between immune cells and the seven hub genes. The subsequent in vitro validation of experimental results showed that downregulating the expression of BIRC5 by siRNA can promote apoptotic activity of SCLC cells and inhibit their vitality, migration, and invasion. The use of BIRC5 inhibitor inhibited the vitality of SCLC cells and increased their apoptotic activity. BIRC5 may be a novel therapeutic target option for SCLC.
Insights
Targeting BIRC5 shows promise for small cell lung cancer (SCLC) treatment. Inhibiting BIRC5 in SCLC cells increases apoptosis and reduces cell viability, migration, and invasion, suggesting it as a novel therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Small cell lung cancer (SCLC) is a highly malignant neuroendocrine tumor.
- Current treatments (immunotherapy + chemotherapy) face challenges due to rapid resistance and relapse.
- Identifying novel therapeutic targets for SCLC is crucial.
Purpose of the Study:
- To identify potential novel therapeutic targets for SCLC.
- To investigate the role of differentially expressed genes and immune cell infiltration in SCLC.
- To validate the therapeutic potential of identified target genes in vitro.
Main Methods:
- Analysis of four Gene Expression Omnibus microarray datasets.
- Differential gene expression screening using batch correction and RobustRankAggregation.
- Protein-protein interaction network construction and hub gene identification using Cytoscape and CytoHubba algorithms.
- Immune cell infiltration analysis using LASSO regression and Wilcoxon test.
- In vitro validation of BIRC5 targeting using siRNA and inhibitors.
Main Results:
- Seven highly expressed hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, AURKA) were identified in SCLC.
- Significant differences in the infiltration of seven immune cell types were observed between SCLC and normal samples.
- A negative correlation was found between BIRC5 expression and monocyte infiltration.
- Downregulating BIRC5 expression via siRNA or using a BIRC5 inhibitor promoted SCLC cell apoptosis and inhibited cell vitality, migration, and invasion.
Conclusions:
- BIRC5 is a potential novel therapeutic target for SCLC.
- Targeting BIRC5 may offer a new strategy to overcome treatment resistance and improve outcomes in SCLC patients.
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