Title |
Downregulation of dystroglycan glycosyltransferases LARGE2 and ISPD associate with increased mortality in clear cell renal cell carcinoma
|
---|---|
Published in |
Molecular Cancer, July 2015
|
DOI | 10.1186/s12943-015-0416-z |
Pubmed ID | |
Authors |
Michael R. Miller, Deqin Ma, James Schappet, Patrick Breheny, Sarah L. Mott, Nadine Bannick, Eric Askeland, James Brown, Michael D. Henry |
Abstract |
Dystroglycan (DG) is a cell-surface laminin receptor that links the cytoskeleton to the extracellular matrix in a variety of epithelial tissues. Its function as a matrix receptor requires extensive glycosylation of its extracellular subunit αDG, which involves at least 13 distinct genes. Prior work has shown loss of αDG glycosylation in an assortment of carcinomas, including clear cell renal cell carcinoma (ccRCC) though the cause (s) and functional consequences of this loss are still unclear. Using The Cancer Genome Atlas (TCGA) database, we analyzed the DG glycosylation pathway to identify changes in mRNA expression and correlation with clinical outcomes. We validated our findings with a cohort of 65 patients treated with radical nephrectomy by analyzing DG glycosylation via immunohistochemistry and gene expression via qRT-PCR. Analysis of TCGA database revealed frequent dysregulation of a subset of DG glycosyltransferases. Most notably, there was a frequent, significant downregulation of GYLTL1B (LARGE2) and ISPD. DG glycosylation is frequently impaired in ccRCC patient samples and most strongly associates with downregulation of GYLTL1B. Reduced levels of GYLTL1B and ISPD mRNA associated with increased patient mortality and are the likely cause of αDG hypoglycosylation in ccRCC. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Spain | 1 | 4% |
Unknown | 24 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 4 | 16% |
Student > Master | 4 | 16% |
Student > Doctoral Student | 3 | 12% |
Other | 2 | 8% |
Lecturer | 1 | 4% |
Other | 5 | 20% |
Unknown | 6 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 4 | 16% |
Agricultural and Biological Sciences | 4 | 16% |
Biochemistry, Genetics and Molecular Biology | 2 | 8% |
Immunology and Microbiology | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 4 | 16% |
Unknown | 8 | 32% |