Expression of serum‑ and glucocorticoid‑regulated kinase 1 and its association with clinicopathological factors and the survival of patients with adenocarcinoma of the esophagogastric junction

Gao,Shegan; Wang,Dan; Kong,Guoqiang; Li,Shuoguo; Wang,Wei; Wang,Huizhi; Zhou,Fuyou

doi:10.3892/ol.2017.5927

Expression of serum‑ and glucocorticoid‑regulated kinase 1 and its association with clinicopathological factors and the survival of patients with adenocarcinoma of the esophagogastric junction

Authors:
- Shegan Gao
- Dan Wang
- Guoqiang Kong
- Shuoguo Li
- Wei Wang
- Huizhi Wang
- Fuyou Zhou
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Affiliations: Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine and Medical College of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China, Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY 40202, USA, Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan 455000, P.R. China
Published online on: March 27, 2017 https://doi.org/10.3892/ol.2017.5927
Pages: 3572-3578
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

While the aberrant expression and the controversial results of serum‑ and glucocorticoid‑regulated kinase (SGK1) have been reported in a number of malignancies, the expression of SGK1 and its possible association with the progression of adenocarcinoma in the esophagogastric junction (AEG) remain to be elucidated. To the best of our knowledge, the expression and localization of SGK1 was examined for the first time in the present study in cancerous and adjacent tissue from 60 patients with AEG, and compared with 20 healthy mucosa control tissue samples. Furthermore, the association between SGK1 expression and the clinicopathological characteristics, and prognosis of patients with AEG was statistically analyzed. The expression level of SGK1 was identified to be significantly higher (P<0.0001) in the cancerous AEG tissue samples (65%) compared with that of the adjacent tissue (31.7%) and healthy control (10%) samples. Enhanced SGK1 was primarily localized in the cytoplasm and the expression level of SGK1 was associated with the differentiation (P=0.045) and lymph node metastasis (P=0.006) of AEG. Notably, increased expression of SGK1 was demonstrated to be significantly correlated with poor overall survival (P=0.027). The results of the present study revealed the expression profile of SGK1 in AEG and demonstrated that SGK1 expression in cancerous tissue is an indicator for the progression of AEG. Thus, SGK1 may be a potential molecular marker for the diagnosis, interference therapy and prognosis of AEG.

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1	Engstrom PF, Arnoletti JP, Benson AB III, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, et al: NCCN clinical practice guidelines in oncology: Colon cancer. J Natl Compr Canc Netw. 7:778–831. 2009.PubMed/NCBI
2	Liu K, Zhang W, Chen X, Chen X, Yang K, Zhang B, Chen Z, Zhou Z and Hu J: Comparison on clinicopathological features and prognosis between esophagogastric junctional adenocarcinoma (Siewert II/III Types) and distal gastric adenocarcinoma: Retrospective cohort study, a single institution, high volume experience in china. Medicine (Baltimore). 94:e13862015. View Article : Google Scholar : PubMed/NCBI
3	Vial M, Grande L and Pera M: Epidemiology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third. Recent Results Cancer Res. 182:1–17. 2010. View Article : Google Scholar : PubMed/NCBI
4	Buas MF and Vaughan TL: Epidemiology and risk factors for gastroesophageal junction tumors: Understanding the rising incidence of this disease. Semin Radiat Oncol. 23:3–9. 2013. View Article : Google Scholar : PubMed/NCBI
5	Siewert JR, Feith M and Stein HJ: Biologic and clinical variations of adenocarcinoma at the esophago-gastric junction: Relevance of a topographic-anatomic subclassification. J Surg Oncol. 90:139–146. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lang F, Böhmer C, Palmada M, Seebohm G, Strutz-Seebohm N and Vallon V: (Patho) physiological significance of the serum-and glucocorticoid-inducible kinase isoforms. Physiol Rev. 86:1151–1178. 2006. View Article : Google Scholar : PubMed/NCBI
7	Lang F and Cohen P: Regulation and physiological roles of serum-and glucocorticoid-induced protein kinase isoforms. Sci STKE. 2001:re172001.PubMed/NCBI
8	Brunet A, Park J, Tran H, Hu LS, Hemmings BA and Greenberg ME: Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol. 21:952–965. 2001. View Article : Google Scholar : PubMed/NCBI
9	Lang F, Henke G, Embark HM, Waldegger S, Palmada M, Böhmer C and Vallon V: Regulation of channels by the serum and glucocorticoid-inducible kinase-implications for transport, excitability and cell proliferation. Cell Physiol Biochem. 13:41–50. 2003. View Article : Google Scholar : PubMed/NCBI
10	Nasir O, Wang K, Föller M, Gu S, Bhandaru M, Ackermann TF, Boini KM, Mack A, Klingel K, Amato R, et al: Relative resistance of SGK1 knockout mice against chemical carcinogenesis. IUBMB Life. 61:768–776. 2009. View Article : Google Scholar : PubMed/NCBI
11	Sommer EM, Dry H, Cross D, Guichard S, Davies BR and Alessi DR: Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors. Biochem J. 452:499–508. 2013. View Article : Google Scholar : PubMed/NCBI
12	Abbruzzese C, Mattarocci S, Pizzuti L, Mileo AM, Visca P, Antoniani B, Alessandrini G, Facciolo F, Amato R, D'Antona L, et al: Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas. J Exp Clin Cancer Res. 31:42012. View Article : Google Scholar : PubMed/NCBI
13	Talarico C, D'Antona L, Scumaci D, Barone A, Gigliotti F, Fiumara CV, Dattilo V, Gallo E, Visca P, Ortuso F, et al: Preclinical model in HCC: The SGK1 kinase inhibitor SI113 blocks tumor progression in vitro and in vivo and synergizes with radiotherapy. Oncotarget. 6:37511–37525. 2015.PubMed/NCBI
14	Rauhala HE, Porkka KP, Tolonen TT, Martikainen PM, Tammela TL and Visakorpi T: Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer. Int J Cancer. 117:738–745. 2005. View Article : Google Scholar : PubMed/NCBI
15	Chu S, Rushdi S, Zumpe ET, Mamers P, Healy DL, Jobling T, Burger HG and Fuller PJ: FSH-regulated gene expression profiles in ovarian tumours and normal ovaries. Mol Hum Reprod. 8:426–433. 2002. View Article : Google Scholar : PubMed/NCBI
16	Ronchi CL, Sbiera S, Leich E, Tissier F, Steinhauer S, Deutschbein T, Fassnacht M and Allolio B: Low SGK1 expression in human adrenocortical tumors is associated with ACTH-independent glucocorticoid secretion and poor prognosis. J Clin Endocrinol Metab. 97:E2251–E2260. 2012. View Article : Google Scholar : PubMed/NCBI
17	Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Störkel S, et al: EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: Analysis of data from the phase 3 FLEX study. Lancet Oncol. 13:33–42. 2012. View Article : Google Scholar : PubMed/NCBI
18	Webster MK, Goya L, Ge Y, Maiyar AC and Firestone GL: Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol Cell Biol. 13:2031–2040. 1993. View Article : Google Scholar : PubMed/NCBI
19	Park J, Leong ML, Buse P, Maiyar AC, Firestone GL and Hemmings BA: Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI3-kinase-stimulated signaling pathway. EMBO J. 18:3024–3033. 1999. View Article : Google Scholar : PubMed/NCBI
20	Kobayashi T and Cohen P: Activation of serum-and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem J. 339:319–328. 1999. View Article : Google Scholar : PubMed/NCBI
21	Mundi PS, Sachdev J, McCourt C and Kalinsky K: AKT in cancer: New molecular insights and advances in drug development. Br J Clin Pharmacol. 82:943–956. 2016. View Article : Google Scholar : PubMed/NCBI
22	Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A and Kuchroo VK: Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 496:513–517. 2013. View Article : Google Scholar : PubMed/NCBI
23	Zhou H, Gao S, Duan X, Liang S, Scott DA, Lamont RJ and Wang H: Inhibition of serum-and glucocorticoid-inducible kinase 1 enhances TLR-mediated inflammation and promotes endotoxin-driven organ failure. FASEB J. 29:3737–3749. 2015. View Article : Google Scholar : PubMed/NCBI
24	Gu Z, Lamont GJ, Lamont RJ, Uriarte SM, Wang H and Scott DA: Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes. Innate Immun. 22:186–195. 2016. View Article : Google Scholar : PubMed/NCBI
25	Bhatelia K, Singh K and Singh R: TLRs: Linking inflammation and breast cancer. Cell Signal. 26:2350–2357. 2014. View Article : Google Scholar : PubMed/NCBI
26	Gao S, Brown J, Wang H and Feng X: The role of glycogen synthase kinase 3-β in immunity and cell cycle: Implications in esophageal cancer. Arch Immunol Ther Exp (Warsz). 62:131–144. 2014. View Article : Google Scholar : PubMed/NCBI
27	Dehner M, Hadjihannas M, Weiske J, Huber O and Behrens J: Wnt signaling inhibits Forkhead box O3a-induced transcription and apoptosis through up-regulation of serum-and glucocorticoid-inducible kinase 1. J Biol Chem. 283:19201–19210. 2008. View Article : Google Scholar : PubMed/NCBI
28	Huang H and Tindall DJ: Dynamic FoxO transcription factors. J Cell Sci. 120:2479–2487. 2007. View Article : Google Scholar : PubMed/NCBI
29	You H, Jang YJ, You-Ten AI, Okada H, Liepa J, Wakeham A, Zaugg K and Mak TW: p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1. Proc Natl Acad Sci USA. 101:14057–14062. 2004. View Article : Google Scholar : PubMed/NCBI
30	Brunet A, Park J, Tran H, Hu LS, Hemmings BA and Greenberg ME: Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol. 21:952–965. 2001. View Article : Google Scholar : PubMed/NCBI
31	Borst O, Schaub M, Walker B, Schmid E, Münzer P, Voelkl J, Alesutan I, Rodríguez JM, Vogel S, Schoenberger T, et al: Pivotal role of serum-and glucocorticoid-inducible kinase 1 in vascular inflammation and atherogenesis. Arterioscler Thromb Vasc Biol. 35:547–557. 2015. View Article : Google Scholar : PubMed/NCBI
32	Mikosz CA, Brickley DR, Sharkey MS, Moran TW and Conzen SD: Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J Biol Chem. 276:16649–16654. 2001. View Article : Google Scholar : PubMed/NCBI