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Published on: June 16, 2018
Significant downregulation of platelet gene expression in metastatic lung cancer
David C Calverley1, Tzu L Phang, Qamrul G Choudhury
1Division of Medical Oncology, University of Colorado Denver, USA. calverle@ohsu.edu
Abstract:
Platelets play a major role in the metastatic dissemination of tumor cells in vivo . Recent evidence reveals megakaryocyte-derived platelet pre-mRNA is spliced to mRNA and then translated into functional proteins in response to external stimulation. Employing a human lung cancer model, we hypothesized a subset of megakaryocyte/platelet genes exists that are significantly over or underexpressed in metastasis compared with noncancer. Microarray analysis employing platelet mRNA followed by unsupervised hierarchical clustering revealed an expression profile that includes decreased expression of 197 of the 200 platelet genes with the most altered expression (p < 1.0 × 10(-4)). Among the 608 splicing events identified between the metastasis and negative control groups, 33 highly variable genes were identified with between 3 and 13 splicing events each. In conclusion, this preliminary study reveals a platelet-based gene expression signature that differentiates metastatic lung cancer from negative controls on the basis of decreased expression of 197 of the 200 genes with the most altered expression levels. Further study may yield a prognostic tool for future metastasis among subsets of early stage lung cancer patients.
Insights
This study found a unique gene expression signature in platelets that distinguishes metastatic lung cancer from non-cancerous conditions. This platelet gene signature may help predict future metastasis in early-stage lung cancer patients.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- Platelets are crucial for tumor cell metastasis.
- Megakaryocyte-derived platelet mRNA is processed into functional proteins upon stimulation.
Purpose of the Study:
- To identify megakaryocyte/platelet genes with altered expression in metastatic lung cancer compared to non-cancerous samples.
- To investigate gene splicing events associated with lung cancer metastasis.
Main Methods:
- Microarray analysis of platelet mRNA from lung cancer metastasis and control groups.
- Unsupervised hierarchical clustering to identify gene expression patterns.
- Analysis of gene splicing events between metastatic and control groups.
Main Results:
- A significant decrease in the expression of 197 out of 200 highly altered platelet genes was observed in metastatic lung cancer (p < 1.0 × 10(-4)).
- 33 highly variable genes with 3 to 13 splicing events each were identified between metastatic and control groups.
Conclusions:
- A platelet-based gene expression signature, characterized by decreased expression of specific platelet genes, can differentiate metastatic lung cancer.
- This finding suggests a potential prognostic tool for predicting metastasis in early-stage lung cancer patients.
