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Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression
Authors
Abnet
Alarmo
+43 more
Basic-Jukic
Corradini
Crowley
Dai
Darby
Deligezer
Gazzerro
Hardwick
Helms
Hongo
Hu
Jemal
Jorissen
Kautz
Kersten
Kowanetz
Kusu
Lee
Li
Li
Milano
Miyoshi
Mizuno
Morita
Mulder
Ohba
Peters
Que
Raida
Smith
Sulzbacher
Sutherland
Taylor
Thawani
Valdimarsdottir
Varga
Wang
Wieder
Yanagita
Ying
Yuen
Yuen
Yuen
Publication date
1 January 2012
Publisher
'Wiley'
Doi
Cite
Abstract
Emerging evidence has indicated a role of the bone morphogenetic proteins (BMP) in the pathogenesis of certain cancers. The signaling of BMP family members is tightly regulated by their antagonists, including noggin and SOST, which are, in turn, positively regulated by BMP, thereby forming a negative feedback loop. Consequently, the expression of these antagonists should be taken into account in studies on the prognostic significance of BMP. In the present paper, we correlated protein and mRNA expression levels of BMP6, noggin and SOST, alone or in combination, with patient survival in various types of cancer. We found that BMP6 alone was not significantly correlated with esophageal squamous cell carcinoma patient survival. Instead, a high level of inhibitor of differentiation 1, a downstream factor of BMP6, was associated with shorter survival in patients whose tumors stained strongly for BMP6. Knockdown of noggin in esophageal cancer cell line EC109, which expresses BMP6 strongly and SOST weakly, enhanced the non-adherent growth of the cells. Noggin and SOST expression levels, when analyzed alone, were not significantly correlated with patient survival. However, high BMP6 activity, defined by strong BMP6 expression coupled with weak noggin or SOST expression, was significantly associated with shorter survival in esophageal squamous cell carcinoma patients. We further confirmed that BMP6 activity could be used as a prognostic indicator in prostate, bladder and colorectal cancers, using publicly available data on BMP6, noggin and SOST mRNA expression and patient survival. Our results strongly suggest that BMP6, noggin and SOST could be used in combination as a prognostic indicator in cancer progression. © 2012 Japanese Cancer Association.link_to_subscribed_fulltex
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info:doi/10.1111%2Fj.1349-7006...
Last time updated on 27/04/2021