The High Expressed Serum Soluble Neural Cell Adhesion Molecule, a High Risk Factor Indicating Hepatic Encephalopathy in Hepatocelular Carcinoma Patients

  • Liu, Tian-Hua (Liver Cancer Institute, Zhongshan Hospital, Fudan University) ;
  • Guo, Kun (Liver Cancer Institute, Zhongshan Hospital, Fudan University) ;
  • Liu, Ri-Qiang (Breast Disease Center, Affiliated Cancer Hospital of Guangxi Medical University) ;
  • Zhang, Shu (Liver Cancer Institute, Zhongshan Hospital, Fudan University) ;
  • Huang, Zhuo-Hui (Liver Cancer Institute, Zhongshan Hospital, Fudan University) ;
  • Liu, Yin-Kun (Liver Cancer Institute, Zhongshan Hospital, Fudan University)
  • Published : 2015.04.29


Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.


  1. Barretina J, Taylor BS, Banerji S, et al (2010). Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet, 42, 715-21.
  2. Bhattacharjee A, Richards WG, Staunton J, et al (2001). Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA, 98, 13790-5.
  3. Biewenga P, Buist MR, Moerland PD, et al (2008). Gene expression in early stage cervical cancer. Gynecol Oncol, 108, 520-6.
  4. Brune V, Tiacci E, Pfeil I, et al (2008). Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. J Exp Med, 205, 2251-68.
  5. Ciecko-Michalska I, Szczepanek M, Slowik A, et al (2012). Pathogenesis of hepatic encephalopathy. Gastroenterol Res Pract, 2012, 642108.
  6. Crabtree JS, Jelinsky SA, Harris HA, et al (2009). Comparison of human and rat uterine leiomyomata: identification of a dysregulated mammalian target of rapamycin pathway. Cancer Res, 69, 6171-8.
  7. Cui J, Chen Y, Chou WC, et al (2011). An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer. Nucleic Acids Res, 39, 1197-207.
  8. Cunningham BA, Hemperly JJ, Murray BA, et al (1987). Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science, 236, 799-806.
  9. D'Errico M, de Rinaldis E, Blasi MF, et al (2009). Genomewide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer, 45, 461-9.
  10. Dyrskjot L, Kruhoffer M, Thykjaer T, et al (2004). Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res, 64, 4040-8.
  11. Estilo CL, P Oc, Talbot S, et al (2009). Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis. BMC Cancer, 9, 11.
  12. Ferenci P, Lockwood A, Mullen K, et al (2002). Hepatic encephalopathy-definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology, 35, 716-21.
  13. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.
  14. French PJ, Swagemakers SM, Nagel JH, et al (2005). Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res, 65, 11335-44.
  15. Garber ME, Troyanskaya OG, Schluens K, et al (2001). Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA, 98, 13784-9.
  16. Guo X, Xiong L, Yu L, et al (2014). Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy. Diagn Pathol, 9, 175.
  17. He H, Jazdzewski K, Li W, et al (2005). The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA, 102, 19075-80.
  18. Jensen M, Berthold F (2007). Targeting the neural cell adhesion molecule in cancer. Cancer Lett, 258, 9-21.
  19. Jorgensen OS, Bock E (1974). Brain specific synaptosomal membrane proteins demonstrated by crossed immunoelectrophoresis. J Neurochem, 23, 879-80.
  20. Livingston BD, Jacobs JL, Glick MC, et al (1988). Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells. J Biol Chem, 263, 9443-8.
  21. Mas VR, Maluf DG, Archer KJ, et al (2009). Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med, 15, 85-94.
  22. Munoz SJ (2008). Hepatic encephalopathy. Med Clin North Am, 92, 795-812.
  23. Pode-Shakked N, Metsuyanim S, Rom-Gross E, et al (2009). Developmental tumourigenesis: NCAM as a putative marker for the malignant renal stem/progenitor cell population. J Cell Mol Med, 13, 1792-808.
  24. Rhodes DR, Yu J, Shanker K, et al (2004). ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia, 6, 1-6.
  25. Rutishauser U, Acheson A, Hall AK, et al (1988). The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science, 240, 53-7.
  26. Sabates-Bellver J, Van der Flier LG, de Palo M, et al (2007). Transcriptome profile of human colorectal adenomas. Mol Cancer Res, 5, 1263-75.
  27. Sanchez-Carbayo M, Socci ND, Lozano J, et al (2006). Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol, 24, 778-89.
  28. Sangmala P, Chaikledkaew U, Tanwandee T, et al (2014). Economic evaluation and budget impact analysis of the surveillance program for hepatocellular carcinoma in Thai chronic hepatitis B patients. Asian Pac J Cancer Prev, 15, 8993-9004.
  29. Shan YS, Hsu HP, Lai MD, et al (2015). Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer. Oncol Rep, 33, 49-57.
  30. Sun L, Hui AM, Su Q, et al (2006). Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell, 9, 287-300.
  31. Tsuchiya A, Kamimura H, Takamura M, et al (2009). Clinicopathological analysis of CD133 and NCAM human hepatic stem/progenitor cells in damaged livers and hepatocellular carcinomas. Hepatol Res, 39, 1080-90.
  32. Tsuchiya A, Kamimura H, Tamura Y, et al (2011). Hepatocellular carcinoma with progenitor cell features distinguishable by the hepatic stem/progenitor cell marker NCAM. Cancer Lett, 309, 95-103.
  33. Vilstrup H, Amodio P, Bajaj J, et al (2014). Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American association for the study of liver diseases and the european association for the study of the liver. Hepatology, 60, 715-35.
  34. Welsh JB, Sapinoso LM, Su AI, et al (2001). Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res, 61, 5974-8.
  35. Yoneyama K, Nebashi Y, Kiuchi Y, et al (2004). Prognostic index of cirrhotic patients with hepatic encephalopathy with and without hepatocellular carcinoma. Dig Dis Sci, 49, 1174-80.
  36. Yoshihara K, Tajima A, Komata D, et al (2009). Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis. Cancer Sci, 100, 1421-8.
  37. Zhang ZM, Zhang YM, Gao S, et al (2014). Treatment efficacy and prognostic factors for huge HCC based on barcelona clinic liver cancer staging. Asian Pac J Cancer Prev, 15, 8823-8.
  38. Zhao H, Langerod A, Ji Y, et al (2004). Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol Biol Cell, 15, 2523-36.
  39. Zhu AX (2012). Molecularly targeted therapy for advanced hepatocellular carcinoma in 2012: current status and future perspectives. Semin Oncol, 39, 493-502.

Cited by

  1. Voltage-gated calcium channels: Novel targets for cancer therapy vol.14, pp.2, 2017,