title: Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression.
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.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK. hfyuen@imcb.a-star.edu.sg
authors.forename: Hiu-Fung
authors.initials: HF
authors.lastname: Yuen
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.forename: Claire
authors.initials: C
authors.lastname: Grills
authors.forename: Shu-Dong
authors.initials: SD
authors.lastname: Zhang
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Huang
authors.forename: Ka-Kui
authors.initials: KK
authors.lastname: Chan
authors.forename: Yuen-Piu
authors.initials: YP
authors.lastname: Chan
authors.forename: Michelle Lok-Yee
authors.initials: ML
authors.lastname: Wong
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fennell
authors.forename: Glenn
authors.initials: G
authors.lastname: Dickson
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Tanani
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D005819:Genetic Markers; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099176:Noggin Protein; C422903:SOST protein, human