Bioinformatics Analysis Reveals Significant Genes and Pathways to Targetfor Oral Squamous Cell Carcinoma

  • Jiang, Qian (Department of Stomatology, Zhongshan Hospital, Fudan University) ;
  • Yu, You-Cheng (Department of Stomatology, Zhongshan Hospital, Fudan University) ;
  • Ding, Xiao-Jun (Department of Stomatology, Zhongshan Hospital, Fudan University) ;
  • Luo, Yin (Department of Stomatology, Zhongshan Hospital, Fudan University) ;
  • Ruan, Hong (Department of Stomatology, Zhongshan Hospital, Fudan University)
  • Published : 2014.03.01


Purpose: The purpose of our study was to explore the molecular mechanisms in the process of oral squamous cells carcinoma (OSCC) development. Method: We downloaded the affymetrix microarray data GSE31853 and identified differentially expressed genes (DEGs) between OSCC and normal tissues. Then Gene Ontology (GO) and Protein-Protein interaction (PPI) networks analysis was conducted to investigate the DEGs at the function level. Results: A total 372 DEGs with logFCI >1 and P value < 0.05 were obtained, including NNMT, BAX, MMP9 and VEGF. The enriched GO terms mainly were associated with the nucleoplasm, response to DNA damage stimuli and DNA repair. PPI network analysis indicated that GMNN and TSPO were significant hub proteins and steroid biosynthesis and synthesis and degradation of ketone bodies were significantly dysregulated pathways. Conclusion: It is concluded that the genes and pathways identified in our work may play critical roles in OSCC development. Our data provides a comprehensive perspective to understand mechanisms underlying OSCC and the significant genes (proteins) and pathways may be targets for therapy in the future.


  1. Watanabe H, Iwase M, Ohashi M, Nagumo M (2002). Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines. Oral Oncol, 38, 670-9.
  2. Viswanathan M, Tsuchida N, Shanmugam G (2003). Promoter hypermethylation profile of tumor-associated genes p16, p15, hMLH1, MGMT and E-cadherin in oral squamous cell carcinoma. Int J Cancer, 105, 41-6.
  3. Von Mering C, Huynen M, Jaeggi D, et al (2003a). STRING: a database of predicted functional associations between proteins. Nucleic Acids Res, 31, 258-61.
  4. von Mering C, Huynen M, Jaeggi D, et al (2003b). STRING: a database of predicted functional associations between proteins. Nucleic Acids Res, 31, 258-61.
  5. Wu Y, Siadaty M, Berens M, et al (2008). Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration. Oncogene, 27, 6679-89.
  6. Xing F, Li S, Ge X, et al (2008). The inhibitory effect of a novel organoselenium compound BBSKE on the tongue cancer Tca8113 in vitro and in vivo. Oral Oncol, 44, 963-9.
  7. Yap LF, Jenei V, Robinson CM, et al (2009). Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation. Oncogene, 28, 2524-34.
  8. Shin JA, Jung JY, Ryu MH, et al (2013). Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization. Mol Pharmacol, 83, 33-41.
  9. Pozzi V, Sartini D, Morganti S, et al (2013). RNA-mediated gene silencing of nicotinamide N-Methyltransferase is associated with decreased tumorigenicity in human oral carcinoma cells. PloS One, 8, e71272.
  10. Scott S, Grunfeld E, McGurk M (2005). The idiosyncratic relationship between diagnostic delay and stage of oral squamous cell carcinoma. Oral Oncol, 41, 396-403.
  11. Shandilya J, Swaminathan V, Gadad SS, et al (2009). Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional activation of genes implicated in oral cancer manifestation. Mol Cell Biol, 29, 5115-27.
  12. Spiro RH (1985). Squamous cancer of the tongue. CA Cancer J Clin, 35, 252-6.
  13. Tiziani S, Lopes V, Gunther UL (2009). Early stage diagnosis of oral cancer using 1H NMR-based metabolomics. Neoplasia, 11, 269.
  14. Torres-Rendon A, Roy S, Craig G, Speight P (2009). Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas. Br J Cancer, 100, 1128-34.
  15. Tsai RY, McKay RD (2002). A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev, 16, 2991-3003.
  16. Veech RL (2004). The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids, 70, 309-19.
  17. Loft S, Poulsen H (1996). Cancer risk and oxidative DNA damage in man. J Mol Med, 74, 297-312.
  18. Kim HE, Kim DG, Lee KJ, et al (2012). Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PloS One, 7, e43223.
  19. Landis SH, Murray T, Bolden S, Wingo PA (1999). Cancer statistics, 1999. CA Cancer J Clin, 49, 8-31.
  20. Lo WY, Tsai MH, Tsai Y, et al (2007). Identification of overexpressed proteins in oral squamous cell carcinoma (OSCC) patients by clinical proteomic analysis. Clin Chim Acta, 376, 101-7.
  21. Lyford-Pike S, Peng S, Young GD, et al (2013). Evidence for a role of the PD-1: PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res, 73, 1733-41.
  22. Ma JY, Li M, Ge ZJ, et al (2012). Whole transcriptome analysis of the effects of type I diabetes on mouse oocytes. PloS One, 7, e41981.
  23. Marocchio LS, Giudice F, Correa L, et al (2013). Oestrogens and androgen receptors in oral squamous cell carcinoma. Acta Odontol Scand, 71, 1513-9.
  24. Mashberg A, Samit AM (1989). Early detection, diagnosis, and management of oral and oropharyngeal cancer. CA Cancer J Clin, 39, 67-88.
  25. Nagler R, Ben-Izhak O, Savulescu D, et al (2010). Oral cancer, cigarette smoke and mitochondrial 18kDa translocator protein (TSPO) - In vitro, in vivo, salivary analysis. Biochim Biophys Acta, 1802, 454-61.
  26. Neville B, Damm D, Allen C, Bouquot J (2002). Oral and Maxillofacial Pathology ( (ed 2)) Saunders. Philadelphia, PA, 582-3.
  27. Patel BP, Shah SV, Shukla SN, et al (2007). Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. Head Neck, 29, 564-72.
  28. Gao J, Li X, Jiang J (2013). [The study of serine/threonine kinase signaling pathway-mediated inhibition of proliferation and invasion of oral squamous cell carcinoma transfected with p53 gene]. Hua Xi Kou Qiang Yi Xue Za Zhi, 31, 145-9.
  29. Deyhimi P, Torabinia N, Torabinia A (2013). A comparative study of histological grade and expression of Ki67 protein in oral squamous cell carcinoma in young and old patients. Dental Res J, 10, 514.
  30. Diboun I, Wernisch L, Orengo C A, Koltzenburg M (2006). Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics, 7, 252.
  31. Emanuelli M, Santarelli A, Sartini D, et al (2010). Nicotinamide N-Methyltransferase upregulation correlates with tumour differentiation in oral squamous cell carcinoma. Histol Histopathol, 25, 15.
  32. Harris M, Clark J, Ireland A, et al (2004). The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res, 32, D258-61.
  33. Huang da W, Sherman BT, Lempicki RA (2008). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 4, 44-57.
  34. Huang da W, Sherman BT, Tan Q, et al (2007). The DAVID Gene Functional Classification Tool: a novel biological modulecentric algorithm to functionally analyze large gene lists. Genome Biol, 8, R183.
  35. Irizarry RA, Hobbs B, Collin F, et al (2003). Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 4, 249-64.
  36. Kammerer P, Koch F, Schiegnitz E, et al (2012). Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma. J Oral Pathol Med, 42, 374-81.
  37. Chan G, Boyle JO, Yang EK, et al (1999). Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res, 59, 991-4.
  38. Altermann E, Klaenhammer TR (2005). PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. BMC Genomics, 6, 60.
  39. Batarseh A, Papadopoulos V (2010). Regulation of translocator protein 18kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol, 327, 1-12.
  40. Bose P, Klimowicz A, Kornaga E, et al (2012). Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma. BMC Cancer, 12, 332.
  41. Cheng AN, Jiang SS, Fan CC, et al (2013). Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents. Cancer Lett, 337, 218-25
  42. Costanzo V, Shechter D, Lupardus PJ, et al (2003). An ATRand Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol Cell, 11, 203-13.

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