Upregulated INHBA expression is associated with poor survival in gastric cancer

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.

[1]  A. Neugut,et al.  Epidemiology of gastric cancer. , 2006, World journal of gastroenterology.

[2]  B. Turner International Union Against Cancer (UICC) , 1999 .

[3]  K. Lewis,et al.  Betaglycan binds inhibin and can mediate functional antagonism of activin signalling , 2000, Nature.

[4]  Paola Sebastiani,et al.  Cluster analysis of gene expression dynamics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Steven Gallinger,et al.  Transcriptional cooperation between the transforming growth factor-beta and Wnt pathways in mammary and intestinal tumorigenesis. , 2007, Cancer research.

[6]  Li Mao,et al.  Transcriptomic dissection of tongue squamous cell carcinoma , 2008, BMC Genomics.

[7]  M. Matzuk,et al.  Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions , 2000, Nature Genetics.

[8]  Richard A. Szucs,et al.  TNM Classification of Malignant Tumors. 5th ed , 1998 .

[9]  H. Shibai,et al.  Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Donaldson,et al.  Identification of a Binding Site on the Type II Activin Receptor for Activin and Inhibin* , 2000, The Journal of Biological Chemistry.

[11]  D. Robertson,et al.  The isolation and physiology of inhibin and related proteins. , 1989, Biology of reproduction.

[12]  Nam-Soon Kim,et al.  Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  M. Goumans,et al.  Signaling of transforming growth factor-beta family members through Smad proteins. , 2000, European journal of biochemistry.

[14]  Fumiko Itoh,et al.  Signaling of transforming growth factor‐β family members through Smad proteins , 2000 .

[15]  M. Matzuk,et al.  Activins are critical modulators of growth and survival. , 2003, Molecular endocrinology.

[16]  J. Massagué,et al.  Mechanisms of TGF-beta signaling from cell membrane to the nucleus. , 2003, Cell.

[17]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Chelala,et al.  Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays , 2008, Oncogene.

[19]  P. Leung,et al.  Mini ReviewActivin Receptor Signaling , 2004 .

[20]  P. Leung,et al.  Activin receptor signaling. , 2004, Growth factors.

[21]  M. Matzuk,et al.  Genetic analysis of the mammalian transforming growth factor-beta superfamily. , 2002, Endocrine reviews.

[22]  Y. Okamoto,et al.  Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling. , 2007, Oncology reports.

[23]  Y. Doki,et al.  Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis , 2008, British Journal of Cancer.

[24]  Hyun Cheol Chung,et al.  Novel biomarker candidates for gastric cancer. , 2008, Oncology reports.

[25]  Yuan-Yu Wang,et al.  Systems biology approach to identification of biomarkers for metastatic progression in gastric cancer , 2009, Journal of Cancer Research and Clinical Oncology.

[26]  Peter W. Andrews,et al.  Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes , 2006, Cellular oncology : the official journal of the International Society for Cellular Oncology.

[27]  M. Itakura,et al.  Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants. , 1998, The Journal of clinical investigation.

[28]  Mads Thomassen,et al.  Gene expression meta‐analysis identifies chromosomal regions involved in ovarian cancer survival , 2009, Genes, chromosomes & cancer.

[29]  K. Miyazono,et al.  Two major Smad pathways in TGF‐β superfamily signalling , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[30]  C. Molloy,et al.  Novel cardiovascular actions of the activins. , 1999, The Journal of endocrinology.

[31]  M. Seto,et al.  Genome‐wide analysis of DNA copy number alterations and gene expression in gastric cancer , 2008, The Journal of pathology.

[32]  D. Beer,et al.  Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma. , 2009, Neoplasia.

[33]  H. Burger,et al.  Inhibin: definition and nomenclature, including related substances. , 1988, Clinical endocrinology.

[34]  G. Serio,et al.  Gene expression analysis of early and advanced gastric cancers , 2007, Oncogene.

[35]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.