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Article: Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression
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TitleCombinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression
 
AuthorsYuen, HF3 1 2
Mccrudden, CM3
Grills, C3
Zhang, SD3
Huang, YH1
Chan, KK3
Chan, YP2
Wong, MLY2
Law, S2
Srivastava, G2
Fennell, DA3
Dickson, G3
ElTanani, M3
Chan, KW2
 
Issue Date2012
 
PublisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
 
CitationCancer Science, 2012, v. 103 n. 6, p. 1145-1154 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1349-7006.2012.02252.x
 
AbstractEmerging 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.
 
ISSN1347-9032
 
DOIhttp://dx.doi.org/10.1111/j.1349-7006.2012.02252.x
 
ISI Accession Number IDWOS:000304758200024
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYuen, HF
 
dc.contributor.authorMccrudden, CM
 
dc.contributor.authorGrills, C
 
dc.contributor.authorZhang, SD
 
dc.contributor.authorHuang, YH
 
dc.contributor.authorChan, KK
 
dc.contributor.authorChan, YP
 
dc.contributor.authorWong, MLY
 
dc.contributor.authorLaw, S
 
dc.contributor.authorSrivastava, G
 
dc.contributor.authorFennell, DA
 
dc.contributor.authorDickson, G
 
dc.contributor.authorElTanani, M
 
dc.contributor.authorChan, KW
 
dc.date.accessioned2012-10-30T06:26:37Z
 
dc.date.available2012-10-30T06:26:37Z
 
dc.date.issued2012
 
dc.description.abstractEmerging 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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationCancer Science, 2012, v. 103 n. 6, p. 1145-1154 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1349-7006.2012.02252.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1349-7006.2012.02252.x
 
dc.identifier.epage1154
 
dc.identifier.hkuros206233
 
dc.identifier.isiWOS:000304758200024
 
dc.identifier.issn1347-9032
 
dc.identifier.issue6
 
dc.identifier.pmid22364398
 
dc.identifier.scopuseid_2-s2.0-84861691253
 
dc.identifier.spage1145
 
dc.identifier.urihttp://hdl.handle.net/10722/173026
 
dc.identifier.volume103
 
dc.languageeng
 
dc.publisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
 
dc.publisher.placeJapan
 
dc.relation.ispartofCancer Science
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshAged, 80 And Over
 
dc.subject.meshBone Morphogenetic Protein 6 - Genetics - Metabolism
 
dc.subject.meshBone Morphogenetic Proteins - Genetics - Metabolism
 
dc.subject.meshCarcinoma, Squamous Cell - Genetics - Mortality
 
dc.subject.meshCarrier Proteins - Genetics - Metabolism
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshColorectal Neoplasms - Metabolism
 
dc.subject.meshDisease Progression
 
dc.subject.meshEsophageal Neoplasms - Genetics - Mortality - Pathology
 
dc.subject.meshFemale
 
dc.subject.meshGenetic Markers - Genetics
 
dc.subject.meshHumans
 
dc.subject.meshInhibitor Of Differentiation Protein 1 - Metabolism
 
dc.subject.meshMale
 
dc.subject.meshMiddle Aged
 
dc.subject.meshProstatic Neoplasms - Metabolism
 
dc.subject.meshRna Interference
 
dc.subject.meshRna, Messenger - Genetics - Metabolism
 
dc.subject.meshRna, Small Interfering
 
dc.subject.meshSignal Transduction
 
dc.subject.meshUrinary Bladder Neoplasms - Metabolism
 
dc.titleCombinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression
 
dc.typeArticle
 
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Author Affiliations
  1. Institute of Molecular and Cell Biology, A-Star, Singapore
  2. The University of Hong Kong
  3. Queen's University Belfast