Going to the AACR Annual Meeting? Visit our poster to find out more about a novel biomarker candidate for cancer!
The genome of a healthy person is constantly interacting with external signals and internal cues to adapt to a changing environment. Similarly, tumors also respond to the therapies aimed at removing them; chemotherapy and targeted molecular therapies can occasionally induce additional mutations or gene expression changes in tumor genomes. These secondary genetic changes are associated with increased drug resistance, recurrent forms of cancer and poorer chances of survival for patients.
Our presentation at the AACR Annual Meeting next week focuses on the correlations we identified for one such gene, sorting nexin 9 (SNX9). NextBio analysis of data correlations to SNX9 revealed several correlations of the gene to multiple types of cancer, including breast, prostate and other cancers.
SNX9 is a member of the sorting nexin family of proteins. Sorting nexins are typically located in the cytoplasm of cells, where some of them are involved with protein sorting and intracellular trafficking functions. SNX9 in particular is involved with regulating cellular levels of the EGFR protein by interacting with cdc kinase. EGFR is a more familiar player to cancer researchers, with several drugs available that are specifically designed to inhibit EGFR expression in tumors, such as erlotinib.
Our explorations of public data found several studies linking changes in SNX9 methylation, expression or mutations in the gene to different cancer types.The figure below shows the number of NextBio studies for SNX9 correlated to cancer organized by data type; directions on the graph indicate the way a particular data type is changed in cancer. For example, RNA expression of SNX9 is decreased in several hundred studies of cancer in humans and mice. A few studies of human miRNA changes show an increase of SNX9-targeting microRNAs like miR-453-9p in certain cancer types.
Disease Atlas: NextBio data types correlated with SNX9 in cancer.
Several of these studies correlated loss of SNX9 with more aggressive or recurrent disease. We also used Pharmaco Atlas to analyze how anti-cancer drugs currently used in the clinic affected SNX9. Taken together, our analyses suggest that SNX9 could play a role in cancer progression. Interestingly, a recent paper by Mao et al. describes a genomic fusion of SNX9 with the tumor suppressor UNC5C in prostate cancer. They report that this chromosomal rearrangement causes a loss of function of both genes, suggesting a role for SNX9 in prostate carcinogenesis.
An older blog post by Dan Koboldt also describes a study of changes in lung cancer genomes before and after treatment. According to his post, the presentation at AGBT 2010 described research at the BC Cancer Genome Agency where scientists compared the genomic profile of lung cancer before and after treatment. Non-small cell lung cancer (NSCLC) patients enrolled in the clinical trial first received erlotinib, an EGFR inhibitor. The researchers extracted DNA and RNA from tumor biopsy samples before and after treatment, to see which genes were significantly different. A small set of genes, including SNX9, were mutated in tumors only after treatment, suggesting that these genes could be involved in more progressive forms of the disease.
Identifying biomarkers that can predict how a cancer will progress, or respond to particular therapies is critical to developing targeted molecular therapies or simply being able to monitor a patient’s disease. To hear more about our results on this potential biomarker candidate, stop by our poster at the meeting. Dr. Joe Delaney from our Curation team will be presenting our results on April 3, 2012, in a poster titled, “Identification of a potential tumor suppressor function for SNX9 by mining public genomic data”.
Can’t make it to the meeting? Contact us for more information about the presentation.
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