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, HF1 2 3
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
2011 Impact Factor: 3.325
2011 SCImago Journal Rankings: 0.442
DOIhttp://dx.doi.org/10.1111/j.1349-7006.2012.02252.x
ReferencesReferences in Scopus
DC Field
Value
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.issn1347-9032
2011 Impact Factor: 3.325
2011 SCImago Journal Rankings: 0.442
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
Author Affiliations
  1. Institute of Molecular and Cell Biology, A-Star, Singapore
  2. The University of Hong Kong
  3. Queen's University Belfast