HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells.

Abstract
Dysregulated apoptotic pathways are regarded as major reasons for chemoresistance development as a particular challenge in ovarian cancer therapy. In search of molecular factors affecting human ovarian cancer cell apoptosis and, consequently, patient survival, we examined tumors of 103 platinum-/taxane-treated ovarian cancer patients by mRNA-array hybridization, qPCR, and immunohistochemistry. We identified high expression of crystallin αB (CRYAB), a proposed negative regulator of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. By Kaplan Meier analysis, this factor turned out to be significantly associated with poor patient outcome [overall survival (OS) p = 0.001, recurrence-free survival (RFS) p = 0.003]. Elevated hazard ratios (HR) were estimated with regard to OS (HR = 2.11, 95% CI 1.10-4.06) and RFS (HR = 1.92, 95% CI 1.07-3.47) in multivariable analyses. These associations were confirmed in independent, publicly available mRNA data comprising 431 patients for OS (p < 0.001) and 413 for RFS (p < 0.001). Our findings were validated by studying apoptotic events in cultured human ovarian cancer cells which were stably transfected to express elevated CRYAB levels. These data emphasized the crucial role of CRYAB in human ovarian cancer biology since TRAIL- as well as cisplatin-induced apoptosis was significantly impaired as a function of enhanced CRYAB expression. Taken together, we identified CRYAB as an independent biomarker for unfavourable outcome of human ovarian cancer patients. Since TRAIL is currently tested as anti-cancer drug and large proportions of the present patient cohort displayed low CRYAB levels in their tumors, CRYAB may enable the selection of patient subgroups benefiting most from TRAIL-containing therapy.
AuthorsJuliane Volkmann, Ute Reuning, Martina Rudelius, Norman Häfner, Tibor Schuster, Aaron Becker V Ros, Joerg Weimer, Felix Hilpert, Marion Kiechle, Matthias Dürst, Norbert Arnold, Barbara Schmalfeldt, Alfons Meindl, Juliane Ramser
JournalInternational journal of cancer (Int J Cancer) Vol. 132 Issue 12 Pg. 2820-32 (Jun 15 2013) ISSN: 1097-0215 [Electronic] United States
PMID23225306 (Publication Type: Journal Article)
CopyrightCopyright © 2012 UICC.
Chemical References
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Messenger
  • TNF-Related Apoptosis-Inducing Ligand
  • alpha-Crystallin B Chain
  • Caspase 3
  • Cisplatin
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Biomarkers, Tumor (genetics, metabolism)
  • Caspase 3 (metabolism)
  • Cell Line, Tumor
  • Cisplatin (pharmacology)
  • Enzyme Activation (drug effects)
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms (genetics, mortality, pathology)
  • Prognosis
  • RNA, Messenger (genetics, metabolism)
  • TNF-Related Apoptosis-Inducing Ligand (pharmacology)
  • alpha-Crystallin B Chain (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: