The first 4 authors contributed equally to this work.
Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value
A large Chinese study based on tissue microarray
Version of Record online: 10 APR 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 12, pages 2212–2222, 15 June 2013
How to Cite
Gao, X.-H., Liu, Q.-Z., Chang, W., Xu, X.-D., Du, Y., Han, Y., Liu, Y., Yu, Z.-Q., Zuo, Z.-G., Xing, J.-J., Cao, G. and Fu, C.-G. (2013), Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value. Cancer, 119: 2212–2222. doi: 10.1002/cncr.28052
- Issue online: 4 JUN 2013
- Version of Record online: 10 APR 2013
- Manuscript Accepted: 25 FEB 2013
- Manuscript Received: 4 DEC 2012
- Manuscript Revised: 24 FEB 2012
- zinc finger protein 148 (ZNF148);
- colorectal neoplasms;
- colon neoplasms;
- rectal neoplasms;
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.
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.
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.
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. Cancer 2013;119:2212–2222. © 2013 American Cancer Society.