Prognostic significance of the co‑expression of nucleophosmin and trefoil factor 3 in postoperative gastric cancer patients

Li,Yong; Sun,Zhenqing; Liu,Kewei; Qiu,Wensheng; Yao,Ruyong; Feng,Tongtong; Xin,Chao; Yue,Lu

doi:10.3892/mco.2014.351

Prognostic significance of the co‑expression of nucleophosmin and trefoil factor 3 in postoperative gastric cancer patients

Authors:
- Yong Li
- Zhenqing Sun
- Kewei Liu
- Wensheng Qiu
- Ruyong Yao
- Tongtong Feng
- Chao Xin
- Lu Yue
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Affiliations: Department of Oncology and Tumor Molecular and Translational Medicine Laboratory, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Department of General Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Central Laboratory, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China
Published online on: July 17, 2014 https://doi.org/10.3892/mco.2014.351
Pages: 1055-1061

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Abstract

Although a number of studies have indicated that the positive expression of nucleophosmin (NPM) and trefoil factor 3 (TFF3) is associated with oncogenesis and poor prognosis in several tumor types, the prognostic value of the co‑expression of NPM and TFF3 in gastric cancer (GC) has not been fully elucidated. Therefore, in this study, we aimed to investigate the role of NPM and TFF3 in GC and determine their prognostic value. We retrospectively reviewed 108 patients who had undergone radical gastric tumor resection. The expression of NPM and TFF3 was detected by immunohistochemistry and the association of NPM and TFF3 with clinicopathological characteristics was investigated using the Chi‑square test. Furthermore, univariate and multivariate analyses were conducted to determine the prognostic value of these markers. Of the 108 samples, NPM was positive in 57 (53%) and TFF3 was positive in 54 samples (50%). The positive expression of NPM was correlated with advanced tumor stage and recurrence (P=0.0333 and P<0.0001, respectively), whereas the expression of TFF3 was associated with larger tumor size (P=0.0005), poor differentiation (P=0.0435), lymph node metastasis (P=0.0116), advanced tumor stage (P=0.0244) and recurrence (P=0.0116). The univariate analysis revealed that the expression of NPM, the expression of TFF3 and the co‑expression of the two were associated with poor survival (P=0.0004, 0.0028 and 0.0020, respectively). By multivariate analysis, all three factors were identified as independent prognostic factors in postoperative GC patients (hazard ratio = 1.970, 2.021 and 2.339, respectively). In conclusion, the expression of NPM and TFF3 and, particularly, the co‑expression of the two, may serve as independent prognostic factors in postoperative GC patients.

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1	He W, Tang B, Yang D, et al: Double-positive expression of high-mobility group box 1 and vascular endothelial growth factor C indicates a poorer prognosis in gastric cancer patients. World J Surg Oncol. 11:1612013. View Article : Google Scholar
2	Zhang YZ, Zhang LH, Gao Y, et al: Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling. World J Gastroenterol. 17:1710–1717. 2011. View Article : Google Scholar : PubMed/NCBI
3	Jia YF, Xiao DJ, Ma XL, et al: Differentiated embryonic chondrocyte-expressed gene 1 is associated with hypoxia-inducible factor 1alpha and Ki67 in human gastric cancer. Diagn Pathol. 8:372013. View Article : Google Scholar : PubMed/NCBI
4	Jin J, Jin T, Quan M, Piao Y and Lin Z: Ezrin overexpression predicts the poor prognosis of gastric adenocarcinoma. Diagn Pathol. 7:1352012. View Article : Google Scholar : PubMed/NCBI
5	Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S and Kalantary E: The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays. Diagn Pathol. 7:572012. View Article : Google Scholar : PubMed/NCBI
6	Grisendi S, Mecucci C, Falini B and Pandolfi PP: Nucleophosmin and cancer. Nat Rev Cancer. 6:493–505. 2006. View Article : Google Scholar
7	Khandelwal N, Simpson J, Taylor G, Rafique S, Whitehouse A, Hiscox J and Stark LA: Nucleolar NF-kappaB/RelA mediates apoptosis by causing cytoplasmic relocalization of nucleophosmin. Cell Death Differ. 18:1889–1903. 2011. View Article : Google Scholar : PubMed/NCBI
8	Lin CY, Liang YC and Yung BY: Nucleophosmin/B23 regulates transcriptional activation of E2F1 via modulating the promoter binding of NF-kappaB, E2F1 and pRB. Cell Signal. 18:2041–2048. 2006. View Article : Google Scholar : PubMed/NCBI
9	Nozawa Y, Van Belzen N, Van der Made AC, Dinjens WN and Bosman FT: Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa. J Pathol. 178:48–52. 1996. View Article : Google Scholar : PubMed/NCBI
10	Yun JP, Miao J, Chen GG, et al: Increased expression of nucleophosmin/B23 in hepatocellular carcinoma and correlation with clinicopathological parameters. Br J Cancer. 96:477–484. 2007. View Article : Google Scholar : PubMed/NCBI
11	Subong EN, Shue MJ, Epstein JI, Briggman JV, Chan PK and Partin AW: Monoclonal antibody to prostate cancer nuclear matrix protein (PRO:4–216) recognizes nucleophosmin/B23. Prostate. 39:298–304. 1999.
12	Tsui KH, Cheng AJ, Chang Pe, Pan TL and Yung BY: Association of nucleophosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma. Urology. 64:839–844. 2004. View Article : Google Scholar : PubMed/NCBI
13	Zhang Y: The ARF-B23 connection: implications for growth control and cancer treatment. Cell Cycle. 3:259–262. 2004. View Article : Google Scholar : PubMed/NCBI
14	Mascaux C, Bex F, Martin B, et al: The role of NPM, p14arf and MDM2 in precursors of bronchial squamous cell carcinoma. Eur Respir J. 32:678–686. 2008. View Article : Google Scholar : PubMed/NCBI
15	Tanaka M, Sasaki H, Kino I, Sugimura T and Terada M: Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. Cancer Res. 52:3372–3377. 1992.PubMed/NCBI
16	Muskett FW, May FE, Westley BR and Feeney J: Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins. Biochemistry. 42:15139–15147. 2003. View Article : Google Scholar
17	Katoh M: Trefoil factors and human gastric cancer (Review). Int J Mol Med. 12:3–9. 2003.
18	Meyer zum Buschenfelde D, Hoschutzky H, Tauber R and Huber O: Molecular mechanisms involved in TFF3 peptide-mediated modulation of the E-cadherin/catenin cell adhesion complex. Peptides. 25:873–883. 2004.PubMed/NCBI
19	Chen YH, Lu Y, De Plaen IG, Wang LY and Tan XD: Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells. Biochem Biophys Res Commun. 274:576–582. 2000. View Article : Google Scholar : PubMed/NCBI
20	Leung WK, Yu J, Chan FK, et al: Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. J Pathol. 197:582–588. 2002. View Article : Google Scholar : PubMed/NCBI
21	Yamachika T, Werther JL, Bodian C, et al: Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma. Clin Cancer Res. 8:1092–1099. 2002.PubMed/NCBI
22	Zhou F, Qiu W, Sun L, et al: Clinical significance of nucleophosmin/B23 and human epidermal growth factor receptor 2/neu expressions in gastric cancers. APMIS. 121:582–591. 2013. View Article : Google Scholar : PubMed/NCBI
23	Xu CC, Yue L, Wei HJ, et al: Significance of TFF3 protein and Her-2/neu status in patients with gastric adenocarcinoma. Pathol Res Pract. 209:479–485. 2013. View Article : Google Scholar : PubMed/NCBI
24	Xu D, Huang Y, Geng Q, Guan Y, Li Y, et al: Effect of lymph node number on survival of patients with lymph node-negative gastric cancer according to the 7th edition UICC TNM system. PLoS One. 7:e386812012. View Article : Google Scholar : PubMed/NCBI
25	Ding A, Zhao W, Shi X, et al: Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric cancer. PLoS One. 8:e821362013. View Article : Google Scholar : PubMed/NCBI
26	Tsui KH, Juang HH, Lee TH, Chang PL, Chen CL and Yung BY: Association of nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples. Acta Pharmacol Sin. 29:364–370. 2008. View Article : Google Scholar : PubMed/NCBI
27	Meng JR, Tang HZ, Zhou KZ, Shen WH and Guo HY: TFF3 and survivin expressions associate with a lower survival rate in gastric cancer. Clin Exp Med. 13:297–303. 2013. View Article : Google Scholar : PubMed/NCBI
28	Dhar DK, Wang TC, Tabara H, et al: Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Clin Cancer Res. 11:6472–6478. 2005. View Article : Google Scholar : PubMed/NCBI
29	Tobita H, Kajino K, Inami K, et al: Gene expression profile of DNA binding protein A transgenic mice. Int J Oncol. 29:673–679. 2006.PubMed/NCBI