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Published on: January 19, 2019
Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune
Andrew V Kossenkov1, Anil Vachani, Celia Chang
1The Wistar Institute, Philadelphia, Pennsylvania, USA.
Purpose:
To characterize the interactions of non-small cell lung cancer (NSCLC) tumors with the immune system at the level of mRNA and microRNA (miRNA) expression and to define expression signatures that characterize the presence of a malignant tumor versus a nonmalignant nodule.
Experimental Design:
We have examined the changes of both mRNA and miRNA expression levels in peripheral blood mononuclear cells (PBMC) between paired samples collected from NSCLC patients before and after tumor removal using Illumina gene expression arrays.
Results:
We found that malignant tumor removal significantly changes expression of more than 3,000 protein-coding genes, especially genes in pathways associated with suppression of the innate immune response, including natural killer cell signaling and apoptosis-associated ceramide signaling. Binding sites for the ETS domain transcription factors ELK1, ELK4, and SPI1 were enriched in promoter regions of genes upregulated in the presence of a tumor. Additional important regulators included five miRNAs expressed at significantly higher levels before tumor removal. Repressed protein-coding targets of those miRNAs included many transcription factors, several involved in immunologically important pathways. Although there was a significant overlap in the effects of malignant tumors and benign lung nodules on PBMC gene expression, we identified one gene panel which indicates a tumor or nodule presence and a second panel that can distinguish malignant from nonmalignant nodules.
Conclusions:
A tumor presence in the lung influences mRNA and miRNA expression in PBMC and this influence is reversed by tumor removal. These results suggest that PBMC gene expression signatures could be used for lung cancer diagnosis.
Insights
Lung cancer presence alters gene expression in blood cells, with changes reversing after tumor removal. Blood cell gene signatures may aid in diagnosing non-small cell lung cancer (NSCLC).
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Non-small cell lung cancer (NSCLC) impacts the immune system.
- Understanding molecular changes in response to tumors is crucial for diagnosis.
Purpose of the Study:
- Characterize immune system interactions with NSCLC via mRNA and miRNA expression.
- Define expression signatures for malignant tumors versus nonmalignant nodules.
Main Methods:
- Examined mRNA and miRNA expression in peripheral blood mononuclear cells (PBMC) from NSCLC patients.
- Compared samples before and after tumor removal using gene expression arrays.
Main Results:
- Malignant tumor removal altered over 3,000 protein-coding genes, impacting innate immune response pathways.
- Specific transcription factors and miRNAs were associated with tumor presence.
- Identified gene panels to detect lung nodules and differentiate malignant from nonmalignant ones.
Conclusions:
- Tumor presence influences PBMC gene expression, with effects reversible upon removal.
- PBMC gene expression signatures show potential for lung cancer diagnosis.
