Medical Oncology

, Volume 28, Supplement 1, pp 341–348 | Cite as

Identification of candidate molecular markers of nasopharyngeal Carcinoma by tissue microarray and in situ hybridization

  • Shilong Xiong
  • Qian WangEmail author
  • Lei Zheng
  • Feng Gao
  • Junling Li
orignal paper


To scan differentially expressed genes and to identify candidate molecular markers in nasopharyngeal carcinoma (NPC), we analyzed cDNA microarray data by GenMAPP to find specifically expressed genes in NPC and used tissue microarray and in situ hybridization techniques to confirm our microarray results. Our cDNA microarray results showed that TSPAN-1 and DPP10 genes were down-expressed in NPC, and COX7B and RFC2 genes were over-expressed in NPC. Real-time quantitative reverse transcription-PCR and in situ hybridization (ISH) techniques confirmed that TSPAN-1 and DPP10 genes had only 40.72 and 40.70% positive expression in NPC, but had high positive expression in chronic inflammation of nasopharyngeal mucosa (P < 0.01). However, COX7B and RFC2 genes were high positive rate in NPC (84.24 and 64.53%, respectively) than in normal control tissues. The data suggested that TSPAN-1, DPP10, COX7B and RFC2 genes might be the putative molecular markers of NPC.


Nasopharyngeal carcinoma (NPC) Tissue microarray In situ hybridization Molecular marker 



Nasopharyngeal carcinoma


Tissue microarrays


In situ hybridization


Cytochrome c oxidase subunit VIIb


Replication factor C (activator 1) 2


H2A histone family, member Z


Chaperonin containing TCP1, subunit 2 (beta)


Interferon-induced protein 44


APEX nuclease (multifunctional DNA repair enzyme) 1


General transcription factor IIE, polypeptide 2, beta 34 kDa


Myosin light chain kinase


Tubulin, beta


Zinc finger CCCH-type containing 11A


Tetraspanin 1


Dipeptidyl-peptidase 10


Immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and mu polypeptides


Tripartite motif-containing 26


Mitochondrial ribosomal protein S18B


Aryl-hydrocarbon receptor nuclear translocator 2


SH3 domain-binding glutamic acid-rich protein


HGF activator


Chemokine (C–C motif) receptor 9


Armadillo repeat containing, X-linked 6



The authors thank Dr. Ming Li for guidance in data analysis.

Supplementary material

12032_2010_9727_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)


  1. 1.
    Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):421–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Van Tornout JM, Spruck CH III, Shibata A, et al. Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC. Cancer Epidemiol Biomarkers Prev. 1997;6(7):493–7.PubMedGoogle Scholar
  3. 3.
    Shanmugaratnam K. Nasopharyngeal carcinoma: epidemiology, histopathology and aetiology. Ann Acad Med Singapore. 1980;9(3):289–95.PubMedGoogle Scholar
  4. 4.
    Morrison JA, Gulley ML, Pathmanathan R, Raab-Traub N. Differential signaling pathways are activated in the Epstein-Barr virus-associated malignancies nasopharyngeal carcinoma and Hodgkin lymphoma. Cancer Res. 2004;64(15):5251–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Hildesheim A, Levine PH. Etiology of nasopharyngeal carcinoma: a review. Epidemiol Rev. 1993;15(2):466–85.PubMedGoogle Scholar
  6. 6.
    Chou J, Lin YC, Kim J, et al. Nasopharyngeal carcinoma—review of the molecular mechanisms of tumorigenesis. Head Neck. 2008;30(7):946–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Yang GP, Ross DT, Kuang WW, Brown PO, Weigel RJ. Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. Nucleic Acids Res. 1999;27(6):1517–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang SL, Lan FH, Zhuang YP, et al. Microarray analysis of gene-expression profile in hepatocellular carcinoma cell, BEL-7402, with stable suppression of hLRH-1 via a DNA vector-based RNA interference. Yi Chuan Xue Bao. 2006;33(10):881–91.PubMedGoogle Scholar
  9. 9.
    Missiaglia E, Blaveri E, Terris B, et al. Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis. Int J Cancer. 2004;112(1):100–12.PubMedCrossRefGoogle Scholar
  10. 10.
    Li Y, Tang Y, Ye L, et al. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol. 2003;129(1):43–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Chrysovergis A, Gorgoulis VG, Giotakis I, et al. Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis. Med Oncol. 2010. doi: 10.1007/s12032-010-9522-3.
  12. 12.
    Xue Y-J, Lu Q, Sun Z-X. CD147 overexpression is a prognostic factor and a potential therapeutic target in bladder cancer. Med Oncol. 2010. doi: 10.1007/s12032-010-9582-4.
  13. 13.
    Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet. 2002;31(1):19–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Doniger SW, Salomonis N, Dahlquist KD, Vranizan K, Lawlor SC, Conklin BR. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol. 2003;4(1):R7.PubMedCrossRefGoogle Scholar
  15. 15.
    Shanmugaratnam K, Sobin LH. Histological typing of tumours of the upper respiratory tract and ear. 2nd ed. Berlin; New York: Springer; 1991.Google Scholar
  16. 16.
    Teo P, Leung SF, Yu P, Lee WY, Shiu W. A retrospective comparison between different stage classifications for nasopharyngeal carcinoma. Br J Radiol. 1991;64(766):901–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Liu ZQ, Tian YQ, Hu YF, Li XL, Ma FR, Li GY. Alteration of gene expression during nasopharyngeal carcinogenesis revealed by oligonucleotide microarray after microdissection of tumor tissue and normal epithelia from nasopharynx. Chin Med J (Engl). 2009;122(4):437–43.Google Scholar
  18. 18.
    Zeng ZY, Zhou YH, Zhang WL, et al. Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally regulated Wnt signaling pathway. Hum Pathol. 2007;38(1):120–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Zeng Z, Zhou Y, Xiong W, et al. Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray. J Cancer Res Clin Oncol. 2007;133(2):71–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25(1):25–9.PubMedCrossRefGoogle Scholar
  21. 21.
    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):402–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Fan SQ, Ma J, Zhou J, et al. Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis. Hum Pathol. 2006;37(5):593–605.PubMedCrossRefGoogle Scholar
  23. 23.
    Huang DP, Lo KW, van Hasselt CA, et al. A region of homozygous deletion on chromosome 9p21–22 in primary nasopharyngeal carcinoma. Cancer Res. 1994;54(15):4003–6.PubMedGoogle Scholar
  24. 24.
    Hui AB, Lo KW, Leung SF, et al. Loss of heterozygosity on the long arm of chromosome 11 in nasopharyngeal carcinoma. Cancer Res. 1996;56(14):3225–9.PubMedGoogle Scholar
  25. 25.
    Scholz CJ, Sauer G, Deissler H. Glycosylation of tetraspanin Tspan-1 at four distinct sites promotes its transition through the endoplasmic reticulum. Protein Pept Lett. 2009;16(10):1244–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Scholz CJ, Kurzeder C, Koretz K, et al. Tspan-1 is a tetraspanin preferentially expressed by mucinous and endometrioid subtypes of human ovarian carcinomas. Cancer Lett. 2009;275(2):198–203.PubMedCrossRefGoogle Scholar
  27. 27.
    L’Esperance S, Popa I, Bachvarova M, et al. Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors. Int J Oncol. 2006;29(1):5–24.PubMedGoogle Scholar
  28. 28.
    Liang H, Chen H, Shen Y, et al. A rare polymorphism of the COX7B2 gene in a Cantonese family with nasopharyngeal carcinoma. Sci China C Life Sci. 2004;47(5):449–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Shilong Xiong
    • 1
  • Qian Wang
    • 1
    Email author
  • Lei Zheng
    • 1
  • Feng Gao
    • 2
  • Junling Li
    • 2
  1. 1.Laboratory Medicine Center, Nanfang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of Ultrasound, The Third Xiangya HospitalCentral South UniversityChangshaChina

Personalised recommendations