title: Epigenetic inactivation and tumor-suppressor behavior of NGFR in human colorectal cancer.
abstract: The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor.
  
  
  CONCLUSIONS
  p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer.
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China. Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Zuli
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University Guangzhou, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Huo
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Zihuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Ni
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Lekun
authors.initials: L
authors.lastname: Fang
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Colon and Rectum Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China. wangjply01@sohu.com leiwangyinghu@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Guangdong Institute of Gastroenterology, Guangzhou, P.R. China. Department of Colon and Rectum Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, P.R. China. wangjply01@sohu.com leiwangyinghu@hotmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor