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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer

Authors: Wei-hua Zhou, Fang Tang, Jie Xu, Xing Wu, Zhi-ying Feng, Hai-gang Li, Dong-jun Lin, Chun-kui Shao, Quentin Liu

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial.

Methods

The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152).

Results

The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer.

Conclusions

These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.
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Literature
1.
Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM: Gastric adenocarcinoma: review and considerations for future directions. Annals of surgery. 2005, 241 (1): 27-39.PubMedPubMedCentral
2.
3.
4.
Zheng L, Wang L, Ajani J, Xie K: Molecular basis of gastric cancer development and progression. Gastric Cancer. 2004, 7 (2): 61-77.CrossRefPubMed
5.
Zhang XW, Sheng YP, Li Q, Qin W, Lu YW, Cheng YF, Liu BY, Zhang FC, Li J, Dimri GP, et al: BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer. Molecular cancer. 2010, 9: 40-10.1186/1476-4598-9-40.CrossRefPubMedPubMedCentral
6.
de Maat MF, van de Velde CJ, Umetani N, de Heer P, Putter H, van Hoesel AQ, Meijer GA, van Grieken NC, Kuppen PJ, Bilchik AJ, et al: Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer. J Clin Oncol. 2007, 25 (31): 4887-4894. 10.1200/JCO.2006.09.8921.CrossRefPubMed
7.
Hayashi M, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, Kawano T, Sugihara K: High expression of HER3 is associated with a decreased survival in gastric cancer. Clin Cancer Res. 2008, 14 (23): 7843-7849. 10.1158/1078-0432.CCR-08-1064.CrossRefPubMed
8.
Chatterjee D, Sabo E, Tavares R, Resnick MB: Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: implications for clinical outcome. Clin Cancer Res. 2008, 14 (10): 2994-3001. 10.1158/1078-0432.CCR-07-4496.CrossRefPubMed
9.
Zhao ZS, Wang YY, Chu YQ, Ye ZY, Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2010, 16 (1): 260-268. 10.1158/1078-0432.CCR-09-1247.CrossRefPubMed
10.
De Vita F, Giuliani F, Silvestris N, Catalano G, Ciardiello F, Orditura M: Human epidermal growth factor receptor 2 (HER2) in gastric cancer: a new therapeutic target. Cancer treatment reviews. 2010, 36 (Suppl 3): S11-15.CrossRefPubMed
11.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010, 376 (9742): 687-697. 10.1016/S0140-6736(10)61121-X.CrossRefPubMed
12.
Mhawech P: 14-3-3 proteins--an update. Cell research. 2005, 15 (4): 228-236. 10.1038/sj.cr.7290291.CrossRefPubMed
13.
Pozuelo Rubio M, Geraghty KM, Wong BH, Wood NT, Campbell DG, Morrice N, Mackintosh C: 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal. 2004, 379 (Pt 2): 395-408.CrossRefPubMedPubMedCentral
14.
Fu H, Subramanian RR, Masters SC: 14-3-3 proteins: structure, function, and regulation. Annual review of pharmacology and toxicology. 2000, 40: 617-647. 10.1146/annurev.pharmtox.40.1.617.CrossRefPubMed
15.
Mackintosh C: Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes. The Biochemical journal. 2004, 381 (Pt 2): 329-342.CrossRefPubMedPubMedCentral
16.
Prasad GL, Valverius EM, McDuffie E, Cooper HL: Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells. Cell Growth Differ. 1992, 3 (8): 507-513.PubMed
17.
Ferguson AT, Evron E, Umbricht CB, Pandita TK, Chan TA, Hermeking H, Marks JR, Lambers AR, Futreal PA, Stampfer MR, et al: High frequency of hypermethylation at the 14-3-3 sigma locus leads to gene silencing in breast cancer. Proceedings of the National Academy of Sciences of the United States of America. 2000, 97 (11): 6049-6054. 10.1073/pnas.100566997.CrossRefPubMedPubMedCentral
18.
Iwata N, Yamamoto H, Sasaki S, Itoh F, Suzuki H, Kikuchi T, Kaneto H, Iku S, Ozeki I, Karino Y, et al: Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma. Oncogene. 2000, 19 (46): 5298-5302. 10.1038/sj.onc.1203898.CrossRefPubMed
19.
Osada H, Tatematsu Y, Yatabe Y, Nakagawa T, Konishi H, Harano T, Tezel E, Takada M, Takahashi T: Frequent and histological type-specific inactivation of 14-3-3sigma in human lung cancers. Oncogene. 2002, 21 (15): 2418-2424. 10.1038/sj.onc.1205303.CrossRefPubMed
20.
Lodygin D, Diebold J, Hermeking H: Prostate cancer is characterized by epigenetic silencing of 14-3-3sigma expression. Oncogene. 2004, 23 (56): 9034-9041. 10.1038/sj.onc.1208004.CrossRefPubMed
21.
Akahira J, Sugihashi Y, Suzuki T, Ito K, Niikura H, Moriya T, Nitta M, Okamura H, Inoue S, Sasano H, et al: Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation. Clin Cancer Res. 2004, 10 (8): 2687-2693. 10.1158/1078-0432.CCR-03-0510.CrossRefPubMed
22.
Yi B, Tan SX, Tang CE, Huang WG, Cheng AL, Li C, Zhang PF, Li MY, Li JL, Yi H, et al: Inactivation of 14-3-3 sigma by promoter methylation correlates with metastasis in nasopharyngeal carcinoma. Journal of cellular biochemistry. 2009, 106 (5): 858-866. 10.1002/jcb.22051.CrossRefPubMed
23.
Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Steele D, Cossu A, Budroni M, Palmieri G, Lakhani SR: Distribution and significance of 14-3-3sigma, a novel myoepithelial marker, in normal, benign, and malignant breast tissue. The Journal of pathology. 2004, 202 (3): 274-285. 10.1002/path.1530.CrossRefPubMed
24.
Cheng AL, Huang WG, Chen ZC, Peng F, Zhang PF, Li MY, Li F, Li JL, Li C, Yi H, et al: Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clin Cancer Res. 2008, 14 (2): 435-445. 10.1158/1078-0432.CCR-07-1215.CrossRefPubMed
25.
Neupane D, Korc M: 14-3-3sigma Modulates pancreatic cancer cell survival and invasiveness. Clin Cancer Res. 2008, 14 (23): 7614-7623. 10.1158/1078-0432.CCR-08-1366.CrossRefPubMedPubMedCentral
26.
Li Z, Dong Z, Myer D, Yip-Schneider M, Liu J, Cui P, Schmidt CM, Zhang JT: Role of 14-3-3sigma in poor prognosis and in radiation and drug resistance of human pancreatic cancers. BMC cancer. 2010, 10: 598-10.1186/1471-2407-10-598.CrossRefPubMedPubMedCentral
27.
Perathoner A, Pirkebner D, Brandacher G, Spizzo G, Stadlmann S, Obrist P, Margreiter R, Amberger A: 14-3-3sigma expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Clin Cancer Res. 2005, 11 (9): 3274-3279. 10.1158/1078-0432.CCR-04-2207.CrossRefPubMed
28.
Xie D, Sham JS, Zeng WF, Lin HL, Che LH, Wu HX, Wen JM, Fang Y, Hu L, Guan XY: Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray. International journal of cancer. 2003, 107 (6): 896-902. 10.1002/ijc.11514.CrossRefPubMed
29.
Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A: Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. Journal of clinical pathology. 2007, 60 (10): 1112-1116. 10.1136/jcp.2006.044537.CrossRefPubMed
30.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. The New England journal of medicine. 2001, 345 (10): 725-730. 10.1056/NEJMoa010187.CrossRefPubMed
31.
Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B: 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature. 1999, 401 (6753): 616-620. 10.1038/44188.CrossRefPubMed
32.
Wan XB, Fan XJ, Chen MY, Xiang J, Huang PY, Guo L, Wu XY, Xu J, Long ZJ, Zhao Y, et al: Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma. Autophagy. 2010, 6 (3): 395-404. 10.4161/auto.6.3.11303.CrossRefPubMed
33.
Zurita M, Lara PC, del Moral R, Torres B, Linares-Fernandez JL, Arrabal SR, Martinez-Galan J, Oliver FJ, Ruiz de Almodovar JM: Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC cancer. 2010, 10: 217-CrossRefPubMedPubMedCentral
34.
Ravi D, Chen Y, Karia B, Brown A, Gu TT, Li J, Carey MS, Hennessy BT, Bishop AJ: 14-3-3 sigma expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis. PloS one. 2011, 6 (1): e15864-10.1371/journal.pone.0015864.CrossRefPubMedPubMedCentral
Metadata
Title
Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer
Authors
Wei-hua Zhou
Fang Tang
Jie Xu
Xing Wu
Zhi-ying Feng
Hai-gang Li
Dong-jun Lin
Chun-kui Shao
Quentin Liu
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-397

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