J Gastric Cancer.  2017 Sep;17(3):228-236. 10.5230/jgc.2017.17.e28.

Overexpression of Neuron-Specific Enolase as a Prognostic Factor in Patients with Gastric Cancer

Affiliations
  • 1Department of Surgery, Gyeongsang National University School of Medicine, Jinju, Korea. hongsc@gnu.ac.kr
  • 2Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, Korea. jshgnuh@naver.com
  • 3Institue of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea.
  • 4Department of Anesthesiology, Gyeongsang National University School of Medicine, Jinju, Korea.
  • 5Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Korea.
  • 6Department of Microbiology/Research Institute of Life Science, Gyeongsang National University College of Natural Sciences, Jinju, Korea.
  • 7Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea.

Abstract

PURPOSE
Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC).
MATERIALS AND METHODS
To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells.
RESULTS
In terms of histology as per the World Health Organization criteria (P=0.340), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P<0.010), lymph node metastasis (P=0.010), advanced stage group (P<0.010), cancer-related death (P<0.010), and cancer recurrence (P<0.010). Additionally, a Kaplan-Meier survival analysis revealed that the NSE-OE group had longer cumulative survival times than the NSE-UE group (log-rank test, P<0.010). However, there were no significant differences in the serum levels of NSE expression in patients with GC and healthy volunteers (P=0.280).
CONCLUSIONS
Patients with NSE overexpressing GC tissues showed better prognostic results, implying that NSE could be a candidate biomarker of GC.

Keyword

Stomach neoplasms; Neuron-specific enolase; Neoplasm metastasis; Prognosis

MeSH Terms

Cytoplasm
Healthy Volunteers
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Phosphoenolpyruvate
Phosphopyruvate Hydratase*
Prognosis
Recurrence
Stomach Neoplasms*
World Health Organization
Phosphoenolpyruvate
Phosphopyruvate Hydratase

Figure

  • Fig. 1 Immunohistochemical analysis of NSE expression in GC tissues. NSE = neuron-specific enolase; GC = gastric cancer.

  • Fig. 2 Patients with NSE-OE show longer survival times than patients with NSE-UE according to Kaplan-Meier survival analysis. NSE-OE = neuron-specific enolase overexpression; NSE-UE = neuron-specific enolase underexpression.

  • Fig. 3 Western blot staining to evaluate the NSE level in fresh frozen tumor tissues at each of the TNM stages I to IV. NSE = neuron-specific enolase; TNM = tumor, node, and metastasis; GAPDH = glyceraldehyde-3-phosphate dehydrogenase.

  • Fig. 4 Comparison of quantified serum NSE levels. NSE = neuron-specific enolase; GC = gastric cancer.


Reference

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65:87–108.
2. Lee HJ, Yang HK, Ahn YO. Gastric cancer in Korea. Gastric Cancer. 2002; 5:177–182.
3. Pinson P, Joos G, Watripont P, Brusselle G, Pauwels R. Serum neuron-specific enolase as a tumor marker in the diagnosis and follow-up of small-cell lung cancer. Respiration. 1997; 64:102–107.
4. Cooper EH. Neuron-specific enolase. Int J Biol Markers. 1994; 9:205–210.
5. Kaiser E, Kuzmits R, Pregant P, Burghuber O, Worofka W. Clinical biochemistry of neuron specific enolase. Clin Chim Acta. 1989; 183:13–31.
6. Jørgensen LG, Osterlind K, Hansen HH, Cooper EH. Serum neuron-specific enolase (S-NSE) in progressive small-cell lung cancer (SCLC). Br J Cancer. 1994; 70:759–761.
7. Kimura M, Tsuda H, Morita D, Ichikura T, Ogata S, Aida S, et al. A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based on correlation of fluorescence in situ hybridization and immunohistochemical measurements. Virchows Arch. 2004; 445:255–262.
8. Chen CD, Wang CS, Huang YH, Chien KY, Liang Y, Chen WJ, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance. Proteomics. 2007; 7:155–167.
9. Cho HJ, Baek KE, Park SM, Kim IK, Choi YL, Cho HJ, et al. RhoGDI2 expression is associated with tumor growth and malignant progression of gastric cancer. Clin Cancer Res. 2009; 15:2612–2619.
10. Kim MA, Lee HS, Lee HE, Jeon YK, Yang HK, Kim WH. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number. Histopathology. 2008; 52:738–746.
11. Cho JY. Molecular diagnosis for personalized target therapy in gastric cancer. J Gastric Cancer. 2013; 13:129–135.
12. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, 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; 376:687–697.
13. Corso G, Pedrazzani C, Marrelli D, Pascale V, Pinto E, Roviello F. Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma. Arch Surg. 2009; 144:722–727.
14. Park YS, Jin MY, Kim YJ, Yook JH, Kim BS, Jang SJ. The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann Surg Oncol. 2008; 15:1968–1976.
15. Wu WK, Cho CH, Lee CW, Fan D, Wu K, Yu J, et al. Dysregulation of cellular signaling in gastric cancer. Cancer Lett. 2010; 295:144–153.
16. Xiangming C, Hokita S, Natsugoe S, Tanabe G, Baba M, Takao S, et al. p21 expression is a prognostic factor in patients with p53-negative gastric cancer. Cancer Lett. 2000; 148:181–188.
17. Yu D, Du K, Liu T, Chen G. Prognostic value of tumor markers, NSE, CA125 and SCC, in operable NSCLC Patients. Int J Mol Sci. 2013; 14:11145–11156.
18. Dong Y, Zheng X, Yang Z, Sun M, Zhang G, An X, et al. Serum carcinoembryonic antigen, neuron-specific enolase as biomarkers for diagnosis of nonsmall cell lung cancer. J Cancer Res Ther. 2016; 12:34–36.
19. Sosonkina N, Hong SK, Starenki D, Park JI. Kinome sequencing reveals RET G691S polymorphism in human neuroendocrine lung cancer cell lines. Genes Genomics. 2014; 36:829–841.
20. Lee HS, Kim WH. Tissue array methods for high-throughput clinicopathologic research. Cancer Res Treat. 2006; 38:1–6.
Full Text Links
  • JGC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr