PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target. Surgery 2013 Dec;154(6):1405-16; discussion 1416
Date
11/19/2013Pubmed ID
24238056Pubmed Central ID
PMC4054940DOI
10.1016/j.surg.2013.06.058Scopus ID
2-s2.0-84887862703 (requires institutional sign-in at Scopus site) 58 CitationsAbstract
BACKGROUND: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data for prognostic biomarkers and therapeutic targets.
METHODS: We profiled 44 ACC and 4 normal adrenals on Affymetrix U133 Plus 2 expression microarrays. Pathway and transcriptional enrichment analysis was performed. Protein levels were determined by Western blot. Drug efficacy was assessed against ACC cell lines. Previously published expression datasets were analyzed for validation.
RESULTS: Pathway enrichment analysis identified marked dysregulation of cyclin-dependent kinases and mitosis. Overexpression of PTTG1, which encodes securin, a negative regulator of p53, was identified as a marker of poor survival. Median survival for patients with tumors expressing high PTTG1 levels (log2 ratio of PTTG1 to average β-actin <-3.04) was 1.8 years compared with 9.0 years if tumors expressed lower levels of PTTG1 (P < .0001). Analysis of a previously published dataset confirmed the association of high PTTG1 expression with a poor prognosis. Treatment of 2 ACC cell lines with vorinostat decreased securin levels and inhibited cell growth (median inhibition concentrations of 1.69 μmol/L and 0.891 μmol/L, for SW-13 and H295R, respectively).
CONCLUSION: Overexpression of PTTG1 is correlated with poor survival in ACC. PTTG1/securin is a prognostic biomarker and warrants investigation as a therapeutic target.
Author List
Demeure MJ, Coan KE, Grant CS, Komorowski RA, Stephan E, Sinari S, Mount D, Bussey KJMESH terms used to index this publication - Major topics in bold
Adrenal Cortex NeoplasmsAdrenocortical Carcinoma
Adult
Aged
Antineoplastic Agents
Biomarkers, Tumor
Cell Cycle Checkpoints
Cell Line, Tumor
Female
Gene Expression
Humans
Hydroxamic Acids
Male
Middle Aged
Prognosis
Securin
Tumor Suppressor Protein p53
Young Adult
