Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis.

Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.

[1]  P. Seth,et al.  p27Kip1 is an inducer of intestinal epithelial cell differentiation , 2000 .

[2]  E. Ng,et al.  Allelic Loss of Chromosome 6q in Gastric Carcinoma , 2003, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[3]  N. Carter,et al.  Genomic Profiling Identifies Discrete Deletions Associated with Translocations in Glioblastoma Multiforme , 2006, Cell cycle.

[4]  N. Carter,et al.  Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH , 2006, Oncogene.

[5]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[6]  M. Blaser,et al.  Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. , 1991, The New England journal of medicine.

[7]  Jian Zhang,et al.  Prediction of Colorectal Cancer Relapse and Prognosis by Tissue mRNA Levels of NDRG2 , 2011, Molecular Cancer Therapeutics.

[8]  E. El-Omar,et al.  Helicobacter Pylori associated global gastric cancer burden. , 2009, Frontiers in bioscience.

[9]  K. Abe,et al.  Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma , 2002, Japanese journal of cancer research : Gann.

[10]  C. Cho,et al.  Nicotine and gastric cancer. , 2005, Alcohol.

[11]  E. Wynder,et al.  The decline in gastric cancer: epidemiology of an unplanned triumph. , 1986, Epidemiologic reviews.

[12]  Tin-Lap Lee,et al.  DNA methylation of cancer genome. , 2009, Birth defects research. Part C, Embryo today : reviews.

[13]  J. Beaulieu,et al.  Role of p27(Kip1) in human intestinal cell differentiation. , 2001, Gastroenterology.

[14]  D. Shibata,et al.  Epstein-Barr virus-associated gastric adenocarcinoma. , 1992, The American journal of pathology.

[15]  Guodong Yang,et al.  E2F1 and RNA binding protein QKI comprise a negative feedback in the cell cycle regulation , 2011, Cell cycle.

[16]  S. Larsson,et al.  Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. , 2006, Gastroenterology.

[17]  D. Parkin,et al.  Global cancer statistics in the year 2000. , 2001, The Lancet. Oncology.

[18]  P. Cocco,et al.  Occupational risk factors for gastric cancer: an overview. , 1996, Epidemiologic reviews.

[19]  H. Lee,et al.  Cell-cycle regulators, bcl-2 and NF-kappaB in Epstein-Barr virus-positive gastric carcinomas. , 2005, International journal of oncology.

[20]  Guodong Yang,et al.  RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer. , 2010, Gastroenterology.

[21]  I. Schieren,et al.  Comparative effects of overexpression of p27Kip1 and p21Cip1/Waf1 on growth and differentiation in human colon carcinoma cells , 1999, Oncogene.

[22]  R. Seruca,et al.  Identification of two distinct regions of deletion at 6q in gastric carcinoma , 1995, Genes, chromosomes & cancer.

[23]  S. Richard,et al.  Target RNA motif and target mRNAs of the Quaking STAR protein , 2005, Nature Structural &Molecular Biology.

[24]  Ling Yang,et al.  Incidence and mortality of gastric cancer in China. , 2006, World journal of gastroenterology.

[25]  Hans-Rudolf Hotz,et al.  The Quaking family of RNA-binding proteins: Coordinators of the cell cycle and differentiation , 2010, Cell cycle.