title: Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown.
  
  
  METHODS
  The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo.
  
  
  RESULTS
  The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo.
  
  
  CONCLUSIONS
  Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer.
authors.affiliation: Department of Gastroenterology, Liuzhou traditional Chinese Medical Hospital Guangxi, Liuzhou, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhou
authors.forename: Sheng
authors.initials: S
authors.lastname: Xie
authors.forename: Chunluan
authors.initials: C
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.forename: Liumei
authors.initials: L
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Lichuan
authors.initials: L
authors.lastname: Luo
authors.forename: Jianxuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Daogang
authors.initials: D
authors.lastname: Wang
authors.forename: Lijian
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Nong
authors.initials: N
authors.lastname: Tang
authors.forename: Yunxi
authors.initials: Y
authors.lastname: Ji
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases