title: Expression of BAMBI and its combination with Smad7 correlates with tumor invasion and poor prognosis in gastric cancer.
abstract: Bone morphogenetic proteins and activin membrane-bound inhibitor (BAMBI) and drosophila mothers against decapentaplegic protein 7 (Smad7) are known to negatively regulate the transforming growth factor-β (TGF-β) signaling and play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of BAMBI alone or in combination with Smad7 is associated with the progression of gastric cancer. In the present study, we investigated the expression of BAMBI and Smad7 in 276 cancer tissues and 263 tumor-adjacent tissues from gastric cancer patients, using tissue-microarray-based immunohistochemistry. The expression of BAMBI and Smad7 was significantly higher in cancer tissues than in tumor-adjacent tissues. The expression of BAMBI was significantly correlated with increased depth of invasion (P = 0.010), lymphatic invasion (P < 0.001), lymph node metastasis (P = 0.001), TNM stage (P = 0.008), and decreased differentiation (P = 0.046). The expression of BAMBI was associated with a significantly shorter overall survival (OS) (P = 0.006) and disease-free survival (DFS) (P = 0.011). The combined expression of BAMBI and Smad7 was associated with more invasion and metastasis as well as less survival time in gastric cancer patients. The univariate analysis showed that the expression of BAMBI alone or in combination with Smad7 was significantly associated with the OS and DFS. These findings suggest that BAMBI and Smad7 may cooperatively inhibit the TGF-β signaling, and thus promote the progression of gastric cancer.
authors.affiliation: Department of Gastrointestinal Endoscopy, The First Affiliated Hospital of China Medical University, No. 155, Nanjing north street, Heping District, Shenyang City, Liaoning Province, 110001, China, smjmw@sina.com.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Yu
authors.forename: Qinghuan
authors.initials: Q
authors.lastname: Xiao
authors.forename: Xuren
authors.initials: X
authors.lastname: Sun
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
authors.forename: Mingjun
authors.initials: M
authors.lastname: Sun
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D051906:Smad7 Protein / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C485671:BAMBI protein, human; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta
references.citation: Oncology. 2005;69 Suppl 1:14-6
references.pmid: 16210871
references.citation: J Clin Oncol. 2005 Mar 20;23(9):2078-93
references.pmid: 15774796
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10202-7
references.pmid: 21633009
references.citation: Anticancer Res. 2000 Nov-Dec;20(6B):4489-93
references.pmid: 11205293
references.citation: J Biol Chem. 2002 Oct 18;277(42):39919-25
references.pmid: 12151385
references.citation: PLoS One. 2012;7(4):e35684
references.pmid: 22539990
references.citation: J Biol Chem. 2008 Nov 28;283(48):33053-8
references.pmid: 18838381
references.citation: Oncol Rep. 2004 Jun;11(6):1219-23
references.pmid: 15138559
references.citation: Trends Endocrinol Metab. 2005 Mar;16(2):73-8
references.pmid: 15734148
references.citation: World J Gastroenterol. 2008 Aug 21;14(31):4880-8
references.pmid: 18756595
references.citation: Zhongguo Fei Ai Za Zhi. 2009 Mar 20;12(3):203-7
references.pmid: 20716422
references.citation: Cell. 2000 Oct 13;103(2):295-309
references.pmid: 11057902
references.citation: J Biol Chem. 2004 Feb 20;279(8):6840-6
references.pmid: 14660579
references.citation: Int J Cancer. 1996 Feb 8;65(4):460-5
references.pmid: 8621228
references.citation: Int J Oncol. 2010 Jan;36(1):49-58
references.pmid: 19956832
references.citation: Int J Cancer. 2009 Jul 15;125(2):328-38
references.pmid: 19326429
references.citation: Cell. 2002 Oct 18;111(2):241-50
references.pmid: 12408868
references.citation: Gastroenterology. 2009 Jul;137(1):165-75
references.pmid: 19328798
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Anticancer Res. 2004 Nov-Dec;24(6):3703-9
references.pmid: 15736400
references.citation: Nat Rev Cancer. 2006 Jul;6(7):506-20
references.pmid: 16794634
references.citation: J Surg Res. 2007 May 15;139(2):182-8
references.pmid: 17270215
references.citation: Nature. 1999 Sep 30;401(6752):480-5
references.pmid: 10519551
references.citation: J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402
references.pmid: 10974075
references.citation: Am J Pathol. 2001 Mar;158(3):987-96
references.pmid: 11238046
references.citation: N Engl J Med. 2001 Sep 6;345(10):725-30
references.pmid: 11547741
references.citation: Expert Opin Ther Targets. 2013 Jul;17(7):743-60
references.pmid: 23651053
references.citation: Cytokine Growth Factor Rev. 1996 Jun;7(1):93-102
references.pmid: 8864357
references.citation: Hepatogastroenterology. 2004 Mar-Apr;51(56):396-400
references.pmid: 15086168
references.citation: J Biol Chem. 2009 Oct 30;284(44):30097-104
references.pmid: 19758997
references.citation: Asian Pac J Cancer Prev. 2012;13(10):5161-5
references.pmid: 23244128
references.citation: Biochem Biophys Res Commun. 2006 Feb 17;340(3):758-66
references.pmid: 16380080
references.citation: APMIS. 2012 Feb;120(2):92-100
references.pmid: 22229264
references.citation: J Clin Oncol. 1999 Feb;17(2):607-14
references.pmid: 10080606