Reduced Stratifin Expression Can Serve As an Independent Prognostic Factor for Poor Survival in Patients with Esophageal Squamous Cell Carcinoma
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Stratifin plays an important role in cancer biology by interfering with intracellular signalling pathways and cell-cycle checkpoints. Decreased expression of stratifin gene has been reported to be a poor prognostic indicator in a variety of human malignant tumors.
To clarify the role and prognostic significance of stratifin in esophageal squamous cell carcinoma (ESCC).
The alteration of stratifin messenger RNA (mRNA) and protein was analyzed by reverse-transcription and quantitative real-time polymerase chain reaction (QRT-PCR) and Western blotting in 20 paired ESCC and nonneoplastic esophageal mucosa tissues, respectively. Then, immunohistochemistry (IHC) was used to evaluate expression of stratifin in tissues of 148 ESCC patients (including the former 20 pairs of tissues) and correlate it with clinicopathological parameters and prognosis of ESCC patients.
The stratifin level of mRNA and protein was markedly downregulated in ESCC tissue compared with in corresponding nonneoplastic esophageal epithelium (P < 0.05). Similarly, the positive rate of stratifin protein expression was lower in the esophageal cancer than in paired nonneoplastic esophageal epithelium as detected by IHC (P = 0.007). Statistically, the downregulation of stratifin expression was correlated with tumor infiltration depth (P = 0.003), lymph node metastasis (P = 0.008), distant metastasis (P = 0.013), and lymphovascular invasion (P = 0.007) of ESCC. Furthermore, the reduced stratifin expression was associated with shorter 5-year survival rate of ESCC patients after curative surgery (P < 0.0001). On the basis of univariate and multivariate Cox regression analysis, we found that reduced stratifin expression, T4 stage, lymph node metastasis, and distant metastasis were independent risk factors for worse prognosis in ESCC patients.
The present report indicates that stratifin could be a useful indicator for prognosis of this disease, as well as a potential target for more effective therapy.
- Stoner GD, Gupta A. Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis. 2001;22(11):1737–1746. doi:10.1093/carcin/22.11.1737. CrossRef
- Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. doi:10.3322/canjclin.55.2.74. CrossRef
- Wang W, Shakes DC. Molecular evolution of the 14-3-3 protein family. J Mol Evol. 1996;43(4):384–398. doi:10.1007/BF02339012. CrossRef
- Rosenquist M, Sehnke P, Ferl RJ, Sommarin M, Larsson C. Evolution of the 14-3-3 protein family: does the large number of isoforms in multicellular organisms reflect functional specificity? J Mol Evol. 2000;51(5):446–458.
- Dougherty MK, Morrison DK. Unlocking the code of 14-3-3. J Cell Sci. 2004;117(Pt10):1875–1884. doi:10.1242/jcs.01171. CrossRef
- Fu H, Subramanian RR, Masters SC. 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol. 2000;40:617–647. doi:10.1146/annurev.pharmtox.40.1.617. CrossRef
- MacKintosh C. Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes. Biochem J. 2004;381(Pt2):329–342. doi:10.1042/BJ20031332.
- Mhawech P. 14-3-3 proteins—an update. Cell Res. 2005;15(4):228–236. doi:10.1038/sj.cr.7290291. CrossRef
- Dhar S, Squire JA, Hande MP, Wellinger RJ, Pandita TK. Inactivation of 14-3-3sigma influences telomere behavior and ionizing radiation induced chromosomal instability. Mol Cell Biol. 2000;20(20):7764–7772. doi:10.1128/MCB.20.20.7764-7772.2000. CrossRef
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–408. doi:10.1006/meth.2001.1262. CrossRef
- Perathoner A, Pirkebner D, Brandacher G, et al. 14-3-3sigma expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Clin Cancer Res. 2005;11(9):3274–3279. doi:10.1158/1078-0432.CCR-04-2207. CrossRef
- Gastl G, Spizzo G, Obrist P, Dünser M, Mikuz G. Ep-CAM overexpression in breast cancer as a predictor of survival. Lancet. 2000;356(9246):1981–1982. doi:10.1016/S0140-6736(00)03312-2. CrossRef
- Yan S, Zhou C, Zhang W, et al. β-catenin/TCF pathway upregulates STAT3 expression in human esophageal squamous cell carcinoma. Cancer Lett. 2008;271(1):85–97. doi:10.1016/j.canlet.2008.05.035. CrossRef
- Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag; 2002. doi:10.1007/b97251.
- Iwata N, Yamamoto H, Sasaki S, et al. Frequent hypermethylation of CpG islands and loss of expression of the gene in human hepatocellular carcinoma. Oncogene. 2000;19(46):5298–5302. doi:10.1038/sj.onc.1203898. CrossRef
- Dellambra E, Golisano O, Bondanza S, et al. Downregulation of 14-3-3 prevents clonal evolution and leads to immortalization of primary human keratinocytes. J Cell Biol. 2000;149(5):1117–1130. doi:10.1083/jcb.149.5.1117. CrossRef
- Umbricht CB, Evron E, Gabrielson E, Ferguson A, Marks J, Sukumar S. Hypermethylation of 14-3-3sigma (stratifin) is an early event in breast cancer. Oncogene. 2001;20(26):3348–3353. doi:10.1038/sj.onc.1204438. CrossRef
- Akahira J, Sugihashi Y, Suzuki T, et al. Decreased expression of 14-3-3sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation. Clin Cancer Res. 2004;10(8):2687–2693. doi:10.1158/1078-0432.CCR-03-0510. CrossRef
- Suzuki H, Itoh F, Toyota M, Kikuchi T, Kakiuchi H, Imai K. Inactivation of the 14-3-3σ gene is associated with 5 V CpG island hypermethylation in human cancers. Cancer Res. 2000;60(16):4353–4357.
- Osada H, Tatematsu Y, Yatabe Y, et al. Frequent and histologic type-specific inactivation of 14-3-3σ in human lung cancers. Oncogene. 2002;21(15):2418–2424. doi:10.1038/sj.onc.1205303. CrossRef
- Logsdon CD, Simeone DM, Binkley C, et al. Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res. 2003;63(10):2649–2657.
- Ito Y, Miyoshi E, Uda E, et al. 14-3-3sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid. Cancer Lett. 2003;200(2):161–166. doi:10.1016/S0304-3835(03)00282-9. CrossRef
- Moreira JM, Gromov P, Celis JE. Expression of the tumor suppressor protein 14-3-3sigma is down-regulated in invasive transitional cell carcinomas of the urinary bladder undergoing epithelial-to-mesenchymal transition. Mol Cell Proteomics. 2004;3(4):410–419. doi:10.1074/mcp.M300134-MCP200. CrossRef
- Okumura H, Natsugoe S, Matsumoto M, et al. Predictive value of p53 and 14-3-3sigma for the effect of chemoradiationtherapy on esophageal squamous cell carcinoma. J Surg Oncol. 2005;91(1):84–89. doi:10.1002/jso.20279. CrossRef
- Kuroda Y, Aishima S, Taketomi A, et al. 14-3-3σ negatively regulates the cell cycle, and its down-regulation is associated with poor outcome in intrahepatic cholangiocarcinoma. Hum Pathol. 2007;38(7):1014–1022. doi:10.1016/j.humpath.2006.12.014. CrossRef
- Cheng L, Pan CX, Zhang JT, et al. Loss of 14-3-3sigma in prostate cancer and its precursors. Clin Cancer Res;. 2004;10(9):3064–3068. doi:10.1158/1078-0432.CCR-03-0652. CrossRef
- Reduced Stratifin Expression Can Serve As an Independent Prognostic Factor for Poor Survival in Patients with Esophageal Squamous Cell Carcinoma
Digestive Diseases and Sciences
Volume 55, Issue 9 , pp 2552-2560
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
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- Esophageal squamous cell carcinoma
- Prognostic indicator
- Industry Sectors
- Author Affiliations
- 1. Department of Pathology, Xiangya Basic Medical College, Central South University, Changsha, China
- 2. Department of Pathology, Changzhi Medical College, Changzhi, China
- 3. Department of Health Statistics and Epidemiology, Public Health College, Central South University, Changsha, China