题名

The Detection of Tumor Location and Lymph Node Metastasis by Aberrant NXPH1 and NXPH2 Expressions in Pancreatic Ductal Adenocarcinomas

DOI

10.4077/CJP.2016.BAF430

作者

Jong-Shiaw Jin;Wen-Chiuan Tsai

关键词

immunostaining scores ; NXPH1 ; NXPH2 ; pathological stages ; pancreatic carcinoma

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

59卷6期(2016 / 12 / 31)

页次

348 - 354

内容语文

英文

中文摘要

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease associated with a poor prognosis and high morbidity. Early diagnosis and complete tumor removal are still the principal factors extending life expectancy in PDAC patients. Here, the relationship of neurexophillin 1 (NXPH1) and NXPH2 expressions with clinicopathological parameters of PDAC was evaluated. Immunohistochemical analysis of NXPH1 and NXPH2 was performed in one tissue microarray of 96 surgical specimens, including normal pancreatic duct tissue (n = 5), PDACs at various stages of differentiation (n = 77), and pancreatic neuroendocrine tumors (n = 14). The intensity of both NXPH1 and NXPH2 staining was weak in only a small proportion of benign pancreatic ductal epithelial cells and was significantly higher in most PDAC specimens than in non-neoplastic pancreatic tissue specimens. However, no correlation of the expression of these PDAC biomarkers with tumor grades, T, N, and American Joint Committee on Cancer (AJCC) pathologic stages was established. Contrary to our expectation, the immunohistochemical results of NXPH1 and NXPH2 were inversely correlated with N stage in PDAC. NXPH1 and NXPH2 as PDAC biomarkers may be used to identify patients with this tumor, help delineate appropriate surgical margins, and identify lymph node metastasis in imaging studies.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Bayne, L.J.,Beatty, G.L.,Jhala, N.,Clark, C.E.,Rhim, A.D.,Stanger, B.Z.,Vonderheide, R.H.(2012).Tumor-derived granulocytemacrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer.Cancer Cell,21,822-835.
  2. Beglopoulos, V.,Montag-Sallaz, M.,Rohlmann, A.,Piechotta, K.,Ahmad, M.,Montag, D.,Missler, M.(2005).Neurexophilin 3 is highly localized in cortical and cerebellar regions and is functionally important for sensorimotor gating and motor coordination.Mol. Cell. Biol.,25,7278-7288.
  3. Campbell, P.J.,Yachida, S.,Mudie, L.J.,Stephens, P.J.,Pleasance, E.D.,Stebbings, L.A.,Morsberger, L.A.,Latimer, C.,McLaren, S.,Lin, M.L.,McBride, D.J.,Varela, I.,Nik-Zainal, S.A.,Leroy, C.,Jia, M.,Menzies, A.,Butler, A.P.,Teague, J.W.,Griffin, C.A.,Burton, J.,Swerdlow, H.,Quail, M.A.,Stratton, M.R.,Iacobuzio-Donahue, C.,Futreal, P.A.(2010).The patterns and dynamics of genomic instability in metastatic pancreatic cancer.Nature,467,1109-1113.
  4. Chellappa, S.,Hugenschmidt, H.,Hagness, M.,Line, P. D.,Labori, K.J.,Wiedswang, G.,Taskén, K.,Aandahl, E.M.(2015).Regulatory T cells that co-express RORγt and FOXP3 are proinflammatory and immunosuppressive and expand in human pancreatic cancer.Oncoimmunology,5,e1102828.
  5. Chen, J.M.,Ferec, C.(2012).Genetics and pathogenesis of chronic pancreatitis: the 2012 update.Clin. Res. Hepatol. Gastroenterol.,36,334-340.
  6. Cheng, M.F.,Tsai, W.C.,Hsia, K.T.,Yang, Y.S.,Jin, J.S.(2014).Expression of urocortin in pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasia.APMIS,122,147-154.
  7. Faria, C.,Miguéns, J.,Antunes, J.L.,Barroso, C.,Pimentel, J.,Martins Maria do, C.,Moura-Nunes, V.,Roque, L.(2008).Genetic alterations in a papillary glioneuronal tumor.J. Neurosurg. Pediatr.,1,99-102.
  8. Faryna, M.,Konermann, C.,Aulmann, S.,Bermejo, J.L.,Brugger, M.,Diederichs, S.,Rom, J.,Weichenhan, D.,Claus, R.,Rehli, M.,Schirmacher, P.,Sinn, H.P.,Plass, C.,Gerhauser, C.(2012).Genome-wide methylation screen in low-grade breast cancer identifies novel epigenetically altered genes as potential biomarkers for tumor diagnosis.FASEB J.,26,4937-4950.
  9. Gall, T.M.,Wasan, H.,Jiao, L.R.(2015).Pancreatic cancer: current understanding of molecular and genetic aetiologies.Postgrad. Med. J.,91,594-600.
  10. Goonetilleke, K.S.,Siriwardena, A.K.(2007).Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer.Eur. J. Surg. Oncol.,33,266-270.
  11. Graziano, S.,Marchiò, S.,Bussolino, F.,Arese, M.(2013).A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2.Biochem. Biophys. Res. Commun.,432,574-579.
  12. Hines, M.,Nielsen, L.,Cooper-White, J.(2008).The hematopoietic stem cell niche: what are we trying to replicate?.J. Chem. Technol. Biotechnol.,83,421-443.
  13. Hong, S.M.,Vincent, A.,Kanda, M.,Leclerc, J.,Omura, N.,Borges, M.,Klein, A.P.,Canto, M.I.,Hruban, R.H.,Goggins, M.(2012).Genome-wide CpG island profiling of intraductal papillary mucinous neoplasms of the pancreas.Clin. Cancer Res.,18,700-712.
  14. Jones, S.,Hruban, R.H.,Kamiyama, M.,Borges, M.,Zhang, X.,Parsons, D.W.,Lin, J.C.,Palmisano, E.,Brune, K.,Jaffee, E.M.,Iacobuzio-Donahue, C.A.,Maitra, A.,Parmigiani, G.,Kern, S.E.,Velculescu, V.E.,Kinzler, K.W.,Vogelstein, B.,Eshleman, J.R.,Goggins, M.,Klein, A.P.(2009).Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.Science,324,217.
  15. Kim, H.R.,Lee, C.H.,Kim, Y.W.,Han, S.K.,Shim, Y.S.,Yim, J.J.(2009).Increased CA 19-9 level in patients without malignant disease.Clin. Chem. Lab. Med.,47,750-754.
  16. Kinzfogl, J.,Hangoc, G.,Broxmeyer, H.E.(2011).Neurexophilin 1 suppresses the proliferation of hematopoietic progenitor cells.Blood,118,565-575.
  17. Knight, J.A.,Skol, A.D.,Shinde, A.,Hastings, D.,Walgren, R.A.,Shao, J.,Tennant, T.R.,Banerjee, M.,Allan, J.M.,Le Beau, M.M.,Larson, R.A.,Graubert, T.A.,Cox, N.J.,Onel, K.(2009).Genomewide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility.Blood,113,5575-5582.
  18. Knutson, K.L.,Curiel, T.J.,Salazar, L.,Disis, M.L.(2003).Immunologic principles and immunotherapeutic approaches in ovarian cancer.Hematol. Oncol. Clin. North Am.,17,1051-1073.
  19. Korsse, S.E.,Harinck, F.,van Lier, M.G.,Biermann, K.,Offerhaus, G.J.,Krak, N.,Looman, C.W.,van Veelen, W.,Kuipers, E.J.,Wagner, A.,Dekker, E.,Mathus-Vliegen, E.M.,Fockens, P.,van Leerdam, M.E.,Bruno, M.J.(2013).Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance.J. Med. Genet.,50,59-64.
  20. Lise, M.F.,El-Husseini, A.(2006).The neuroligin and neurexin families: from structure to function at the synapse.Cell. Mol. Life Sci.,63,1833-1849.
  21. Missler, M.,Südhof, T.C.(1998).Neurexophilins form a conserved family of neuropeptide-like glycoproteins.J. Neurosci.,18,3630-3638.
  22. Murakami, K.(2011).FDG-PET for hepatobiliary and pancreatic cancer: advances and current limitations.World J. Clin. Oncol.,2,229-236.
  23. Pandharipande, P.V.,Jeon, A.,Heberle, C.R.,Dowling, E.C.,Kong, C.Y.,Chung, D.C.,Brugge, W.R.,Hur, C.(2015).Screening for pancreatic adenocarcinoma in BRCA2 mutation carriers: results of a disease simulation model.EBioMedicine,2,1980-1986.
  24. Reynolds, R.B.,Folloder, J.(2014).Clinical management of pancreatic cancer.J. Adv. Pract. Oncol.,5,356-364.
  25. Roberts, N.J.,Klein, A.P.(2013).Genome-wide sequencing to identify the cause of hereditary cancer syndromes: with examples from familial pancreatic cancer.Cancer Lett,340,227-233.
  26. Ross, W.A.,Wasan, S.M.,Evans, D.B.,Wolff, R.A.,Trapani, L.V.,Staerkel, G.A.,Prindiville, T.,Lee, J.H.(2008).Combined EUS with FNA and ERCP for the evaluation of patients with obstructive jaundice from presumed pancreatic malignancy.Gastrointest. Endosc.,68,461-466.
  27. Rustgi, A.K.(2014).Familial pancreatic cancer: genetic advances.Genes Dev.,28,1-7.
  28. Song、 H.,Ramus, S.J.,Kjaer, S.K.,DiCioccio, R.A.,Chenevix-Trench, G.,Pearce, C.L.,Hogdall, E.,Whittemore, A.S.,McGuire, V.,Hogdall, C.,Blaakaer, J.,Wu, A.H.,Van Den Berg, D.J.,Stram, D.O.,Menon, U.,Gentry-Maharaj, A.,Jacobs, I.J.,Webb, P.M.,Beesley, J.,Chen, X.,Australian Cancer (Ovarian) Study,Australian Ovarian Cancer Study Group,Rossing, M.A.,Doherty, J.A.,Chang-Claude, J.,Wang-Gohrke, S.,Goodman, M.T.,Lurie, G.,Thompson, P.J.,Carney, M.E.,Ness, R.B.,Moysich, K.,Goode, E.L.,Vierkant, R.A.,Cunningham, J.M.,Anderson, S.,Schildkraut, J.M.,Berchuck, A.,Iversen, E.S.,Moorman, P.G.,Garcia-Closas, M.,Chanock, S.,Lissowska, J.,Brinton, L.,Anton-Culver, H.,Ziogas, A.,Brewster, W.R.,Ponder, B.A.,Easton, D.F.,Gayther, S.A.,Pharoah, P.D.,Ovarian Cancer Association Consortium(2009).Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.Hum. Mol. Genet.,18,2297-2304.
  29. Sugita, S.,Saito, F.,Tang, J.,Satz, J.,Campbell, K.,Südhof, T.C.(2001).A stoichiometric complex of neurexins and dystroglycan in brain.J. Cell. Biol.,154,435-445.
  30. Sun, Y.(2016).Tumor microenvironment and cancer therapy resistance.Cancer Lett.,380,205-215.
  31. Tsai, W.C.,Lee, H.S.,Nieh, S.,Yang, Y.S.,Hueng, D.Y.(2013).Cortactin and fascin-1 correlate with WHO grades in primary brain tumors.J. Med. Sci.,33,21-27.
  32. Warnat, P.,Oberthuer, A.,Fischer, M.,Westermann, F.,Eils, R.,Brors, B.(2007).Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes.BMC Cancer,7,89.
  33. Wouters, M.M.,Lambrechts, D.,Knapp, M.,Cleynen, I.,Whorwell, P.,Agréus, L.,Dlugosz, A.,Schmidt, P.T.,Halfvarson, J.,Simrén, M.,Ohlsson, B.,Karling, P.,Van Wanrooy, S.,Mondelaers, S.,Vermeire, S.,Lindberg, G.,Spiller, R.,Dukes, G.,D'Amato, M.,Boeckxstaens, G.(2014).Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome.Gut,63,1103-1111.