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| Status |
Public on Feb 20, 2014 |
| Title |
Gene expression changes associated with prognosis of Merkel cell carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Purpose: Due to the rarity of Merkel Cell Carcinoma (MCC), prospective clinical trials have not been practical. This study seeks to identify biomarkers to differentiate between patients with a good and poor prognosis.
Methods: Patients were stratified into good, moderate or poor prognosis. Merkel cell carcinoma (MCC) patients were stratified into one of three groups based upon status 24 months following treatment. Poor prognosis patients either presented with or progressed to distant metastasis. Patients with favorable prognosis had local disease presentation with no subsequent recurrence or nodal disease at presentation with no progression during follow-up of longer than 24 months. Moderate prognosis had recurrent local disease, development of nodal metastasis, or nodal disease at presentation with no progression during follow-up of fewer than 24 months. Using ArcturusXT Laser Capture Microdissection (Molecular Devices), tumor cells were isolated from the specific areas of interest. The captured tumor tissue was subjected to RNA extraction using the Invitrogen PureLink™ FFPE RNA Isolation Kit. The extracted RNA was analyzed for integrity with the Agilent Bioanalyzer then amplified and hybridized to Affymetrix GeneChip Human Exon 1.0 ST arrays using the NuGEN WT- Ovation™ FFPE System.
Results: A total of 191 genes showed significant differential expression (p≤0.05 and 1.5-fold cutoff) between the different between the good and poor prognosis groups. Keratin 20 (KRT20) and Neurofilament protein (NEFM) have been identified in previous studies as proteins of interest in MCC. Our study showed these genes to be significantly upregulated in patients with a poor prognosis. Of interest, phospholipase A2, group X was upregulated in poor responders. Phospholipases liberate arachidonic acid from cellular membranes which can be metabolized to eicosanoids through three major pathways: the cyclooxygenase (COX), the lipoxygenase (LOX) and the cytochrome P450 monooxygenase pathways. This pathway has been implicated in several cancers.
Conclusions: The study identified genes with a previous association with MCC as well as some novel genes. These genes provide the basis for further research into possible biomarkers that will enable the differentiation between patients with a good and poor prognosis.
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| Overall design |
Using laser capture microdissection, tumor cells of patients with a good (n=5), moderate (n=3), and poor prognosis (n=7) were isolated from paraffin embedded archival tissue of 15 patients with Merkel cell carcinoma. Affymetrix Human Exon 1.0ST microarrays were utilized to compare gene expression signatures from good and poor prognosis patients.
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| Contributor(s) |
Masterson L, Thibodeau BJ, Fortier LE, Geddes TJ, Pruetz BL, Keidan R, Wilson GD |
| Citation |
Loren Masterson, Bryan J. Thibodeau, Laura E. Fortier, Timothy J. Geddes, Barbara L. Pruetz, Rajwant Malhotra, Richard Keidan, and George D. Wilson. Gene Expression Differences Predict Treatment Outcome of Merkel Cell Carcinoma Patients. Journal of Skin Cancer, vol. 2014, Article ID 596459, 10 pages, 2014. doi:10.1155/2014/596459
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| Submission date |
Feb 29, 2012 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Bryan Thibodeau |
| E-mail(s) |
bryan.thibodeau@beaumont.edu
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| Phone |
248-551-0275
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| Organization name |
Beaumont Research Institute
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| Department |
BioBank
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| Street address |
3811 West 13 Mile Road
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| City |
Royal Oak |
| State/province |
MI |
| ZIP/Postal code |
48073 |
| Country |
USA |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA152891 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36150_RAW.tar |
293.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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