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Erschienen in: Medical Oncology 1/2012

01.03.2012 | Original Paper

Upregulated INHBA expression is associated with poor survival in gastric cancer

verfasst von: Quan Wang, Yu-Gang Wen, Da-Peng Li, Jun Xia, Chong-Zhi Zhou, Dong-Wang Yan, Hua-Mei Tang, Zhi-Hai Peng

Erschienen in: Medical Oncology | Ausgabe 1/2012

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Abstract

Expression microarrays are widely used for investigating the candidate molecular targets in human cancer. While genome-wide expression signatures screened by gene set enrichment analysis (GSEA) were not performed in Chinese gastric cancer (GC). To gain new molecular targets for GC, GSEA analysis was performed. In the present study, GSEA were used to pick out differentially expressed gene sets of our database. Total RNA of paired tissue samples (n = 48) and a tissue microarray containing 132 paired tissues were used to further validate expression levels of INHBA and its correction with clinicopathological factors. Upregulated INHBA expression in gastric cancer was screened and further confirmed by qPCR and immunostaining analysis. Increased INHBA expression was significantly correlated with the diameter of cancer and depth of tumor invasion. Patients with higher expression levels of INHBA had a shorter disease-free survival rate. It was effective to gain new molecular targets for GC by GSEA analysis. INHBA may be a poor survival indicator of GC.
Literatur
1.
Zurück zum Zitat Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMed Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMed
2.
Zurück zum Zitat Shimizu S, Seki N, Sugimoto T, Horiguchi S, Tanzawa H, et al. Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling. Oncol Rep. 2007;18:1489–97.PubMed Shimizu S, Seki N, Sugimoto T, Horiguchi S, Tanzawa H, et al. Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling. Oncol Rep. 2007;18:1489–97.PubMed
3.
Zurück zum Zitat Takeno A, Takemasa I, Doki Y, Yamasaki M, Miyata H, et al. Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. Br J Cancer. 2008;99:1307–15.PubMedCrossRef Takeno A, Takemasa I, Doki Y, Yamasaki M, Miyata H, et al. Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. Br J Cancer. 2008;99:1307–15.PubMedCrossRef
4.
Zurück zum Zitat Eisen MB, Spellman PT, Brown PO, Botstein D. Clustering analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 1998;95:14863–8.PubMedCrossRef Eisen MB, Spellman PT, Brown PO, Botstein D. Clustering analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 1998;95:14863–8.PubMedCrossRef
5.
Zurück zum Zitat Ramoni MF, Sebastiani P, Kohane IS. Cluster analysis of gene expression dynamics. Proc Natl Acad Sci USA. 2002;99:9121–6.PubMedCrossRef Ramoni MF, Sebastiani P, Kohane IS. Cluster analysis of gene expression dynamics. Proc Natl Acad Sci USA. 2002;99:9121–6.PubMedCrossRef
6.
Zurück zum Zitat Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.PubMedCrossRef Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.PubMedCrossRef
7.
Zurück zum Zitat Sobin LH, Wittekind CH (eds). TNM classification of malignant tumors. 5th ed. International union against cancer (UICC). New York: Wiley; 1997. p. 59–62. Sobin LH, Wittekind CH (eds). TNM classification of malignant tumors. 5th ed. International union against cancer (UICC). New York: Wiley; 1997. p. 59–62.
8.
Zurück zum Zitat Wang YY, Ye ZY, Zhao ZS, Tao HQ, Li SG. Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer. J Cancer Res Clin Oncol. 2010;136:135–41.PubMedCrossRef Wang YY, Ye ZY, Zhao ZS, Tao HQ, Li SG. Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer. J Cancer Res Clin Oncol. 2010;136:135–41.PubMedCrossRef
9.
Zurück zum Zitat Yang S, Chung HC. Novel biomarker candidates for gastric cancer. Oncol Rep. 2008;19:675–80.PubMed Yang S, Chung HC. Novel biomarker candidates for gastric cancer. Oncol Rep. 2008;19:675–80.PubMed
10.
Zurück zum Zitat Tsukamoto Y, Uchida T, Karnan S, Noguchi T, Nguyen LT, et al. Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer. J Pathol. 2008;216:471–82.PubMedCrossRef Tsukamoto Y, Uchida T, Karnan S, Noguchi T, Nguyen LT, et al. Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer. J Pathol. 2008;216:471–82.PubMedCrossRef
11.
Zurück zum Zitat Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, et al. Identification of gastric cancer related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clin Cancer Res. 2005;11:473–82.PubMed Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, et al. Identification of gastric cancer related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clin Cancer Res. 2005;11:473–82.PubMed
12.
Zurück zum Zitat Vecchi M, Nuciforo P, Romagnoli S, Confalonieri S, Pellegrini C, et al. Gene expression analysis of early and advanced gastric cancers. Oncogene. 2007;26:4284–94.PubMedCrossRef Vecchi M, Nuciforo P, Romagnoli S, Confalonieri S, Pellegrini C, et al. Gene expression analysis of early and advanced gastric cancers. Oncogene. 2007;26:4284–94.PubMedCrossRef
13.
Zurück zum Zitat Thomassen M, Jochumsen KM, Mogensen O, Tan Q, Kruse TA. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival. Genes Chromosomes Cancer. 2009;48:711–24.PubMedCrossRef Thomassen M, Jochumsen KM, Mogensen O, Tan Q, Kruse TA. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival. Genes Chromosomes Cancer. 2009;48:711–24.PubMedCrossRef
14.
Zurück zum Zitat Harada T, Chelala C, Bhakta V, Chaplin T, Caulee K, et al. Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays. Oncogene. 2008;27:1951–60.PubMedCrossRef Harada T, Chelala C, Bhakta V, Chaplin T, Caulee K, et al. Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays. Oncogene. 2008;27:1951–60.PubMedCrossRef
15.
Zurück zum Zitat Skotheim RI, Autio R, Lind GE, Kraggerud SM, Andrews PW, et al. Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncol. 2006;28:315–26.PubMed Skotheim RI, Autio R, Lind GE, Kraggerud SM, Andrews PW, et al. Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncol. 2006;28:315–26.PubMed
16.
Zurück zum Zitat Burger HG, Igarashi M. Inhibin: definition and nomenclature, including related substances. Endocrinology. 1988;122:1701–2.PubMedCrossRef Burger HG, Igarashi M. Inhibin: definition and nomenclature, including related substances. Endocrinology. 1988;122:1701–2.PubMedCrossRef
17.
Zurück zum Zitat Murata M, Eto Y, Shibai H, Sakai M, Muramatsu M. Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. Proc Natl Acad Sci USA. 1988;85:2434–8.PubMedCrossRef Murata M, Eto Y, Shibai H, Sakai M, Muramatsu M. Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. Proc Natl Acad Sci USA. 1988;85:2434–8.PubMedCrossRef
18.
Zurück zum Zitat Brown CW, Houston-Hawkins DE, Woodruff TK, Matzuk MM. Insertion of Inhbb into the INHBA locus rescues the INHBA-null phenotype and reveals new activin functions. Nat Genet. 2000;25:453–7.PubMedCrossRef Brown CW, Houston-Hawkins DE, Woodruff TK, Matzuk MM. Insertion of Inhbb into the INHBA locus rescues the INHBA-null phenotype and reveals new activin functions. Nat Genet. 2000;25:453–7.PubMedCrossRef
19.
Zurück zum Zitat Shi Y, Massague J. Mechanisms of TGF-βsignaling from cell membrane to the nucleus. Cell. 2003;113:685–700.PubMedCrossRef Shi Y, Massague J. Mechanisms of TGF-βsignaling from cell membrane to the nucleus. Cell. 2003;113:685–700.PubMedCrossRef
20.
Zurück zum Zitat Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-β superfamily. Endocr Rev. 2002;23:787–823.PubMedCrossRef Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-β superfamily. Endocr Rev. 2002;23:787–823.PubMedCrossRef
21.
Zurück zum Zitat de Kretser DM, Robertson DM. The isolation and physiology of inhibin and related proteins. Biol Reprod. 1989;40:33–47.PubMedCrossRef de Kretser DM, Robertson DM. The isolation and physiology of inhibin and related proteins. Biol Reprod. 1989;40:33–47.PubMedCrossRef
22.
Zurück zum Zitat Yamaoka T, Idehara C, Yano M, Matsushita T, Yamada T, et al. Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. J Clin Invest. 1998;102:294–301.PubMedCrossRef Yamaoka T, Idehara C, Yano M, Matsushita T, Yamada T, et al. Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. J Clin Invest. 1998;102:294–301.PubMedCrossRef
23.
Zurück zum Zitat Molloy CJ, Taylor DS, Pawlowski JE. Novel cardiovascular actions of the activins. J Endocrinol. 1999;161:179–85.PubMedCrossRef Molloy CJ, Taylor DS, Pawlowski JE. Novel cardiovascular actions of the activins. J Endocrinol. 1999;161:179–85.PubMedCrossRef
24.
Zurück zum Zitat Itoh S, Itoh F, Goumans MJ, Ten Dijke P. Signaling of transforming growth factor-beta family members through Smad proteins. Eur J Biochem. 2000;267:6954–67.PubMedCrossRef Itoh S, Itoh F, Goumans MJ, Ten Dijke P. Signaling of transforming growth factor-beta family members through Smad proteins. Eur J Biochem. 2000;267:6954–67.PubMedCrossRef
25.
Zurück zum Zitat Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells. 2002;7:1191–204.PubMedCrossRef Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells. 2002;7:1191–204.PubMedCrossRef
26.
27.
Zurück zum Zitat Gray PC, Greenwald J, Blount AL, Kunitake KS, Donaldson CJ, et al. Identification of a binding site on the Type II activin receptor for activin and inhibin. J Biol Chem. 2000;275:3206–12.PubMedCrossRef Gray PC, Greenwald J, Blount AL, Kunitake KS, Donaldson CJ, et al. Identification of a binding site on the Type II activin receptor for activin and inhibin. J Biol Chem. 2000;275:3206–12.PubMedCrossRef
28.
Zurück zum Zitat Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, et al. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature. 2000;404:411–4.PubMedCrossRef Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, et al. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature. 2000;404:411–4.PubMedCrossRef
29.
Zurück zum Zitat Ye H, Yu T, Temam S, Ziober BL, Wang J et al. Transcriptomic dissection of tongue squamous cell carcinoma. BMC Genomics. 2008; 9:69. Ye H, Yu T, Temam S, Ziober BL, Wang J et al. Transcriptomic dissection of tongue squamous cell carcinoma. BMC Genomics. 2008; 9:69.
30.
Zurück zum Zitat Seder CW, Hartojo W, Lin L, Silvers AL, Wang Z, et al. Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma. Neoplasia. 2009;11:388–96.PubMed Seder CW, Hartojo W, Lin L, Silvers AL, Wang Z, et al. Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma. Neoplasia. 2009;11:388–96.PubMed
31.
Zurück zum Zitat Labbé E, Lock L, Letamendia A, Gorska AE, Gryfe R, et al. Transcriptional cooperation between the transforming growth factor-beta and Wnt pathways in mammary and intestinal tumorigenesis. Cancer Res. 2007;67:75–84.PubMedCrossRef Labbé E, Lock L, Letamendia A, Gorska AE, Gryfe R, et al. Transcriptional cooperation between the transforming growth factor-beta and Wnt pathways in mammary and intestinal tumorigenesis. Cancer Res. 2007;67:75–84.PubMedCrossRef
32.
Zurück zum Zitat Brown CW, Li L, Houston-Hawkins DE, Matzuk MM. Activins are critical modulators of growth and survival. Mol Endocrinol. 2003;17:2404–17.PubMedCrossRef Brown CW, Li L, Houston-Hawkins DE, Matzuk MM. Activins are critical modulators of growth and survival. Mol Endocrinol. 2003;17:2404–17.PubMedCrossRef
Metadaten
Titel
Upregulated INHBA expression is associated with poor survival in gastric cancer
verfasst von
Quan Wang
Yu-Gang Wen
Da-Peng Li
Jun Xia
Chong-Zhi Zhou
Dong-Wang Yan
Hua-Mei Tang
Zhi-Hai Peng
Publikationsdatum
01.03.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 1/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9766-y

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