Ambivalent role of pFAK-Y397 in serous ovarian cancer-a study of the OVCAD consortium
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Ambivalent role of pFAK-Y397 in serous ovarian cancer-a study of the OVCAD consortium. / Aust, Stefanie; Auer, Katharina; Bachmayr-Heyda, Anna; Denkert, Carsten; Sehouli, Jalid; Braicu, Ioana; Mahner, Sven; Lambrechts, Sandrina; Vergote, Ignace; Grimm, Christoph; Horvat, Reinhard; Castillo-Tong, Dan Cacsire; Zeillinger, Robert; Pils, Dietmar.
in: MOL CANCER, Jahrgang 13, 01.01.2014, S. 67.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ambivalent role of pFAK-Y397 in serous ovarian cancer-a study of the OVCAD consortium
AU - Aust, Stefanie
AU - Auer, Katharina
AU - Bachmayr-Heyda, Anna
AU - Denkert, Carsten
AU - Sehouli, Jalid
AU - Braicu, Ioana
AU - Mahner, Sven
AU - Lambrechts, Sandrina
AU - Vergote, Ignace
AU - Grimm, Christoph
AU - Horvat, Reinhard
AU - Castillo-Tong, Dan Cacsire
AU - Zeillinger, Robert
AU - Pils, Dietmar
PY - 2014/1/1
Y1 - 2014/1/1
N2 - BACKGROUND: Focal adhesion kinase (FAK) autophosphorylation seems to be a potential therapeutic target but little is known about the role and prognostic value of FAK and pFAK in epithelial ovarian cancer (EOC). Recently, we validated a gene signature classifying EOC patients into two subclasses and revealing genes of the focal adhesion pathway as significantly deregulated.METHODS: FAK expression and pFAK-Y397 abundance were elucidated by immunohistochemistry and microarray analysis in 179 serous EOC patients. In particular the prognostic value of phosphorylated FAK (pFAK-Y397) and FAK in advanced stage EOC was investigated.RESULTS: Multiple Cox-regression analysis showed that high pFAK abundance was associated with improved overall survival (HR 0.54; p = 0.034). FAK was positive in a total of 92.2% (n = 165) and high pFAK abundance was found in 36.9% (n = 66). High pFAK abundance (36.9% ; n = 66) was associated with either nodal positivity and/or distant metastasis (p = 0.030). Whole genome gene expression data revealed a connection of the FAK-pFAK-Y397 axis and the mTOR-S6K1 pathway, shown to play a major role in carcinogenesis.CONCLUSION: The role of pFAK-Y397 remains controversial: although high pFAK-Y397 abundance is associated with distant and lymph node metastases, it is independently associated with improved overall survival.
AB - BACKGROUND: Focal adhesion kinase (FAK) autophosphorylation seems to be a potential therapeutic target but little is known about the role and prognostic value of FAK and pFAK in epithelial ovarian cancer (EOC). Recently, we validated a gene signature classifying EOC patients into two subclasses and revealing genes of the focal adhesion pathway as significantly deregulated.METHODS: FAK expression and pFAK-Y397 abundance were elucidated by immunohistochemistry and microarray analysis in 179 serous EOC patients. In particular the prognostic value of phosphorylated FAK (pFAK-Y397) and FAK in advanced stage EOC was investigated.RESULTS: Multiple Cox-regression analysis showed that high pFAK abundance was associated with improved overall survival (HR 0.54; p = 0.034). FAK was positive in a total of 92.2% (n = 165) and high pFAK abundance was found in 36.9% (n = 66). High pFAK abundance (36.9% ; n = 66) was associated with either nodal positivity and/or distant metastasis (p = 0.030). Whole genome gene expression data revealed a connection of the FAK-pFAK-Y397 axis and the mTOR-S6K1 pathway, shown to play a major role in carcinogenesis.CONCLUSION: The role of pFAK-Y397 remains controversial: although high pFAK-Y397 abundance is associated with distant and lymph node metastases, it is independently associated with improved overall survival.
U2 - 10.1186/1476-4598-13-67
DO - 10.1186/1476-4598-13-67
M3 - SCORING: Journal article
C2 - 24655477
VL - 13
SP - 67
JO - MOL CANCER
JF - MOL CANCER
SN - 1476-4598
ER -
