title: Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value: a large Chinese study based on tissue microarray.
abstract: BACKGROUND
  It has been speculated that zinc finger protein 148 (ZNF148) is a tumor suppressor. However, to the authors' knowledge, little is known about the clinical significance of ZNF148 expression in patients with colorectal cancer (CRC). The objective of the current study was to clarify the association between ZNF148 expression and the postoperative prognosis of patients with CRC.
  
  
  METHODS
  Tissue microarrays containing 56 normal mucosa, 51 adenoma, 742 CRC (TNM stage I-IV), 16 familial adenomatous polyposis, and 21 metastatic CRC specimens were examined immunohistochemically for ZNF148 expression.
  
  
  RESULTS
  Expression of ZNF148 was found to increase consecutively from normal mucosa to stage I CRC, and then decreased consecutively from stage I to stage IV CRC. Lower expression of ZNF148 in tumors was found to be significantly associated with lymph node metastases, advanced TNM disease stage, poor differentiation, higher rate of disease recurrence, worse overall survival (OS), and shorter disease-free survival. High expression of ZNF148 was also associated with improved OS (P = .025) and disease-free survival (P = .042) in patients with stages II to III CRC. On multivariate Cox analysis, lower ZNF148 expression in tumors, advanced TNM stage, colon cancer, and elevated serum carbohydrate antigen 19-9 (CA19-9) were found to be significant factors for a worse OS. In 16 patients with familial adenomatous polyposis, ZNF148 expression was upregulated at steps toward carcinogenesis. In 21 patients with metastatic CRC, although ZNF148 expression was higher in primary tumors compared with adjacent mucosa, its expression in metastatic tumors was significantly lower than that in primary tumors.
  
  
  CONCLUSIONS
  Although ZNF148 expression is related to colorectal carcinogenesis, high ZNF148 expression in patients with CRC appears to be inversely associated with malignant phenotypes and may serve as a significant prognostic factor after surgery for patients with CRC.
authors.affiliation: Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Gao
authors.forename: Qi-Zhi
authors.initials: QZ
authors.lastname: Liu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Yifang
authors.initials: Y
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Yu
authors.forename: Zhi-Gui
authors.initials: ZG
authors.lastname: Zuo
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Xing
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
authors.forename: Chuan-Gang
authors.initials: CG
authors.lastname: Fu
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011125:Adenomatous Polyposis Coli / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D014408:Biomarkers, Tumor / Q000032:analysis*; D018395:CA-19-9 Antigen / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012016:Reference Values; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human