Browse > Article
http://dx.doi.org/10.5808/gi.20062

Identification of potential candidate genes for lip and oral cavity cancer using network analysis  

Mathavan, Sarmilah (Faculty of Health and Life Sciences, Management and Science University)
Kue, Chin Siang (Faculty of Health and Life Sciences, Management and Science University)
Kumar, Suresh (Faculty of Health and Life Sciences, Management and Science University)
Abstract
Lip and oral cavity cancer, which can occur in any part of the mouth, is the 11th most common type of cancer worldwide. The major obstacles to patients' survival are the poor prognosis, lack of specific biomarkers, and expensive therapeutic alternatives. This study aimed to identify the main genes and pathways associated with lip and oral cavity carcinoma using network analysis and to analyze its molecular mechanism and prognostic significance further. In this study, 472 genes causing lip and oral cavity carcinoma were retrieved from the DisGeNET database. A protein-protein interaction network was developed for network analysis using the STRING database. VEGFA, IL6, MAPK3, INS, TNF, MAPK8, MMP9, CXCL8, EGF, and PTGS2 were recognized as network hub genes using the maximum clique centrality algorithm available in cytoHubba, and nine potential drug candidates (ranibizumab, siltuximab, sulindac, pomalidomide, dexrazoxane, endostatin, pamidronic acid, cetuximab, and apricoxib) for lip and oral cavity cancer were identified from the DGIdb database. Gene enrichment analysis was also performed to identify the gene ontology categorization of cellular components, biological processes, molecular functions, and biological pathways. The genes identified in this study could furnish a new understanding of the underlying molecular mechanisms of carcinogenesis and provide more reliable biomarkers for early diagnosis, prognostication, and treatment of lip and oral cavity cancer.
Keywords
biomarkers; carcinogenesis; lip neoplasms; mouth neoplasms; prognosis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014;8 Suppl 4:S11.   DOI
2 Maruccia M, Onesti MG, Parisi P, Cigna E, Troccola A, Scuderi N. Lip cancer: a 10-year retrospective epidemiological study. Anticancer Res 2012;32:1543-1546.
3 Kerawala C, Roques T, Jeannon JP, Bisase B. Oral cavity and lip cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016;130(S2):S83-S89.
4 Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 2017;67: 51-64.   DOI
5 Gupta B, Bray F, Kumar N, Johnson NW. Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: a case-control study from India. Cancer Epidemiol 2017;51: 7-14.   DOI
6 Salehiniya H, Raei M. Oral cavity and lip cancer in the world: an epidemiological review. Biomed Res Ther 2020;7:3898-3905.   DOI
7 Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, et al. Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer 2000;86:128-131.   DOI
8 Shen LI, Liu L, Yang Z, Jiang N. Identification of genes and signaling pathways associated with squamous cell carcinoma by bioinformatics analysis. Oncol Lett 2016;11:1382-1390.   DOI
9 Pathan M, Keerthikumar S, Ang CS, Gangoda L, Quek CY, Williamson NA, et al. FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics 2015;15:2597-2601.   DOI
10 Baschieri F, Confalonieri S, Bertalot G, Di Fiore PP, Dietmaier W, Leist M, et al. Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis. Nat Commun 2014;5:4839.   DOI
11 Kujan O, van Schaijik B, Farah CS. Immune checkpoint inhibitors in oral cavity squamous cell carcinoma and oral potentially malignant disorders: a systematic review. Cancers (Basel) 2020;12:1937.   DOI
12 von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 2003;31:258-261.   DOI
13 Prior SL, Griffiths AP, Baxter JM, Baxter PW, Hodder SC, Silvester KC, et al. Mitochondrial DNA mutations in oral squamous cell carcinoma. Carcinogenesis 2006;27:945-950.   DOI
14 Park EM, Park YM, Gwak YS. Oxidative damage in tissues of rats exposed to cigarette smoke. Free Radic Biol Med 1998;25:79-86.   DOI
15 Richter C, Park JW, Ames BN. Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A 1988;85:6465-6467.   DOI
16 van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018;19: 213-228.   DOI
17 Xu Q, Zhang Q, Ishida Y, Hajjar S, Tang X, Shi H, et al. EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect. Oncotarget 2017;8:9557-9571.   DOI
18 Weng LP, Wu CC, Hsu BL, Chi LM, Liang Y, Tseng CP, et al. Secretome-based identification of Mac-2 binding protein as a potential oral cancer marker involved in cell growth and motility. J Proteome Res 2008;7:3765-3775.   DOI
19 Goutzanis L, Vairaktaris E, Yapijakis C, Kavantzas N, Nkenke E, Derka S, et al. Diabetes may increase risk for oral cancer through the insulin receptor substrate-1 and focal adhesion kinase pathway. Oral Oncol 2007;43:165-173.   DOI
20 Peisker A, Raschke GF, Fahmy MD, Guentsch A, Roshanghias K, Hennings J, et al. Salivary MMP-9 in the detection of oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2017;22: e270-e275.
21 Peng X, Li W, Johnson WD, Torres KE, McCormick DL. Overexpression of lipocalins and pro-inflammatory chemokines and altered methylation of PTGS2 and APC2 in oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide. PLoS One 2015;10:e0116285.   DOI
22 Jourenkova-Mironova N, Voho A, Bouchardy C, Wikman H, Dayer P, Benhamou S, et al. Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers. Int J Cancer 1999;81:44-48.   DOI
23 Peng Q, Deng Z, Pan H, Gu L, Liu O, Tang Z. Mitogen-activated protein kinase signaling pathway in oral cancer. Oncol Lett 2018;15:1379-1388.
24 Huang GZ, Wu QQ, Zheng ZN, Shao TR, Lv XZ. Identification of candidate biomarkers and analysis of prognostic values in oral squamous cell carcinoma. Front Oncol 2019;9:1054.   DOI
25 Wang J, Wang Y, Kong F, Han R, Song W, Chen D, et al. Identification of a six-gene prognostic signature for oral squamous cell carcinoma. J Cell Physiol 2020;235:3056-3068.   DOI
26 Spangle JM, Roberts TM, Zhao JJ. The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim Biophys Acta Rev Cancer 2017;1868:123-131.   DOI
27 Gasche JA, Hoffmann J, Boland CR, Goel A. Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells. Int J Cancer 2011;129:1053-1063.   DOI
28 Nagler RM, Lischinsky S, Diamond E, Klein I, Reznick AZ. New insights into salivary lactate dehydrogenase of human subjects. J Lab Clin Med 2001;137:363-369.   DOI
29 Bahar G, Feinmesser R, Shpitzer T, Popovtzer A, Nagler RM. Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile. Cancer 2007; 109:54-59.   DOI
30 Jourenkova-Mironova N, Mitrunen K, Bouchardy C, Dayer P, Benhamou S, Hirvonen A. High-activity microsomal epoxide hydrolase genotypes and the risk of oral, pharynx, and larynx cancers. Cancer Res 2000;60:534-536.
31 Lopez-Lazaro M. The Warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med Chem 2008;8:305-312.   DOI
32 Nibali L, Fedele S, D'Aiuto F, Donos N. Interleukin-6 in oral diseases: a review. Oral Dis 2012;18:236-243.   DOI
33 Weiner T, Cance WG. Molecular mechanisms involved in tumorigenesis and their surgical implications. Am J Surg 1994;167:428-434.   DOI
34 Patel KR, Vajaria BN, Begum R, Patel JB, Shah FD, Joshi GM, et al. VEGFA isoforms play a vital role in oral cancer progression. Tumour Biol 2015;36:6321-6332.   DOI
35 Supic G, Jovic N, Zeljic K, Kozomara R, Magic Z. Association of VEGF-A genetic polymorphisms with cancer risk and survival in advanced-stage oral squamous cell carcinoma patients. Oral Oncol 2012;48:1171-1177.   DOI
36 Todd R, Donoff RB, Wong DT. The molecular biology of oral carcinogenesis: toward a tumor progression model. J Oral Maxillofac Surg 1997;55:613-623.   DOI
37 Liu J, Lian X, Liu F, Yan X, Cheng C, Cheng L, et al. Identification of novel key targets and candidate drugs in oral squamous cell carcinoma. Curr Bioinform 2020;15:328-337.   DOI
38 Yang B, Dong K, Guo P, Guo P, Jie G, Zhang G, et al. Identification of key biomarkers and potential molecular mechanisms in oral squamous cell carcinoma by bioinformatics analysis. J Comput Biol 2020;27:40-54.   DOI
39 Ha NH, Park DG, Woo BH, Kim DJ, Choi JI, Park BS, et al. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs. Cytokine 2016;86:64-72.   DOI
40 Sahibzada HA, Khurshid Z, Khan RS, Naseem M, Siddique KM, Mali M, et al. Salivary IL-8, IL-6 and TNF-alpha as potential diagnostic biomarkers for oral cancer. Diagnostics (Basel) 2017;7:21.   DOI
41 Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am 2015;24:491-508.   DOI
42 Gupta B, Kumar N, Johnson NW. Relationship of lifetime exposure to tobacco, alcohol and second hand tobacco smoke with upper aero-digestive tract cancers in India: a case-control study with a life-course perspective. Asian Pac J Cancer Prev 2017; 18:347-356.
43 Pinero J, Queralt-Rosinach N, Bravo A, Deu-Pons J, Bauer-Mehren A, Baron M, et al. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database (Oxford) 2015;2015:bav028.   DOI
44 Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res 2013;41:W77-W83.   DOI