Aim: The aim of this study was to provide a biomarker panel for esophageal, gastric and colorectal cancers. It can help introducing some diagnostic biomarkers for these diseases.
Background: Gastrointestinal cancers (GICs) including esophageal, gastric and colorectal cancers are the most common cancers in the world which are usually diagnosed in the final stages and due to heterogeneity of these diseases, the treatments usually are not successful. For this reason, many studies have been conducted to discover predictive biomarkers.
Methods: In the present study, 507 genes related to esophageal, gastric and colon cancers were extracted.. The network was constructed by Cytoscape software (version 3.4.0). Then a main component of the network was analyzed considering centrality parameters including degree, betweenness, closeness and stress. Three clusters of the protein network accompanied with their seed nodes were determined by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO) analysis of the key genes in combination to the seed nodes was performed.
Results: The network of 17 common differential expressed genes in three esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges were constructed. Eight crucial genes were determined. Three Clusters of the network were analyzed by GO analysis.
Conclusion: The analyses of common genes of the three cancers showed that there are some common crucial genes including TP53, EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to gastrointestinal cancers and can be predictive biomarkers for these cancers.
Keywords: Colon cancer, Gastric cancer, Esophageal cancer, Gene ontology, Biomarker.
Xin Z, Jiang S, Jiang P, Yan X, Fan C, Di S, Wu G, Yang Y, Reiter RJ, Ji G. Melatonin as a treatment for gastrointestinal cancer: a review. Journal of pineal research. 2015; 58(4):375-87.
Zali H, Ahmadi G, Bakhshandeh R, Rezaei-Tavirani M. Proteomic analysis of gene expression during human esophagus cancer. Journal of Paramedical Sciences. 2011; 2(3):37-44.
Visser E, Franken IA, Brosens LA, Ruurda JP, van Hillegersberg R. Prognostic gene expression profiling in esophageal cancer: a systematic review. Oncotarget. 2017; 8(3):5566-77.
Shokrgozar MA, Zali H, Rezaei-Tavirani M, Amanzadeh A. Comparison of Two Staining Assays Trypan Blue and MTT in vitro Evaluation of Human Calprotectin Proliferation Inhibition on Human Gastric Cancer Cells. Trauma Monthly. 2007 ;( 2):127-37.
Siegel R, DeSantis C, Jemal A. Colorectal cancer statistics, 2014. CA: a cancer journal for clinicians. 2014; 64(2):104-17.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. The American journal of gastroenterology. 2015; 110(2):223-62.
Wroblewski LE, Peek RM, Coburn LA. The role of the microbiome in gastrointestinal cancer. Gastroenterology Clinics of North America. 2016; 45(3):543-56.
Genta RM, Lash RH. Helicobacter pylori and Gastrointestinal Polyps. InHelicobacter pylori Research 2016; 28(4):449-54.
Ragnedda G, Disanto G, Giovannoni G, Ebers GC, Sotgiu S, Ramagopalan SV. Protein-protein interaction analysis highlights additional loci of interest for multiple sclerosis. PloS one. 2012; 7(10):e46730.
Tourette C, Li B, Bell R, O'Hare S, Kaltenbach LS, Mooney SD, Hughes RE. A large scale Huntingtin protein interaction network implicates Rho GTPase signaling pathways in Huntington disease. Journal of Biological Chemistry. 2014; 289(10):6709-26.
Rakshit H, Rathi N, Roy D. Construction and analysis of the protein-protein interaction networks based on gene expression profiles of Parkinson's disease. PLoS One. 2014; 9(8):e103047.
Moreno-Gonzalez I, George Edwards III NS, Shahnawaz M, Diaz-Espinoza R, Soto C. Molecular interaction between type 2 diabetes and Alzheimer’s disease through cross-seeding of protein misfolding. Molecular psychiatry. 2017; 22(9): 1327–1334.
Safaei A, Rezaei-Tavirani M, Sobhi S, Akbari ME. Breast cancer biomarker discovery: Proteomics and genomics approaches. Iranian Journal of Cancer Prevention. 2013; 6(11):45-53.
Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati-Rad S, Hasanzadeh H, Rezaei Tavirani M, Seyyedi SS. Protein-Protein Interaction Network could reveal the relationship between the breast and colon cancer. Gastroenterology and Hepatology from Bed to Bench. 2015; 8(3):215-224.
Kuzmanov U, Emili A. Protein-protein interaction networks: probing disease mechanisms using model systems. Genome medicine. 2013; 5(4):37-49.
Gonzalez MW, Kann MG. Protein interactions and disease. PLoS computational biology. 2012; 8(12):e1002819.
Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA. Protein-protein interaction networks (PPI) and complex diseases. Gastroenterology and Hepatology from bed to bench. 2014; 7(1):17-31.
Zamanian–Azodi M, Rezaei–Tavirani M, Hasanzadeh H, Rad SR, Dalilan S. Introducing biomarker panel in esophageal, gastric, and colon cancers; a proteomic approach. Gastroenterology and Hepatology from bed to bench. 2015; 8(1): 6–18.
Ryan DP, Matthews JM. Protein-protein interactions in human disease. Curr Opin Struct Biol. 2005; 15(4):441-6.
Goh KI, Oh E, Jeong H, Kahng B, Kim D. Classification of scale-free networks. Proc Natl Acad Sci U S A. 2002; 99(20):12583-8.
Madhavan B, Yue S, Galli U, Rana S, Gross W, Müller M, Giese NA, Kalthoff H, Becker T, Büchler MW, Zöller M. Combined evaluation of a panel of protein and miRNA serum‐exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. International journal of cancer. 2015; 136(11):2616-27.
Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nature reviews. Cancer. 2013; 13(1):11-26.
Dunyong T, Peizhi T, Jianjun H, Jie Z, Weihua Z, Walker AM. Expression of a constitutively active prolactin receptor causes histone trimethylation of the p53 gene in breast cancer. Chinese medical journal. 2014; 127(6):1077-83.
Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992; 70(6):937-48.
Pandurangan AK. Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev. 2013; 14(4):2201-5.
Melchior B, Frangos JA. Distinctive Subcellular Akt‐1 Responses to Shear Stress in Endothelial Cells. Journal of cellular biochemistry. 2014; 115(1):121-9.
Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nature reviews. Microbiology. 2014; 12(10):661-72.
Fazeli Z, Alebouyeh M, Tavirani MR, Azimirad M, Yadegar A. Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells. Gastroenterology and Hepatology from bed to bench. 2016; 9(1):S42-S46.
Wroblewski LE, Peek RM, Jr., Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010; 23(4):713-39.
Limonta P, Marelli MM, Mai S, Motta M, Martini L, Moretti RM. GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies. Endocrine reviews. 2012 Jul 9; 33(5):784-811.
Glunde K, Penet MF, Jiang L, Jacobs MA, Bhujwalla ZM. Choline metabolism-based molecular diagnosis of cancer: an update. Expert review of molecular diagnostics. 2015 Jun 3; 15(6):735-47.
Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nature reviews. Drug discovery. 2005; 4(12):988 -1004.
Hsueh YS, Yen CC, Shih NY, Chiang NJ, Li CF, Chen LT. Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors. Autophagy. 2013; 9(2):220-33.
Khayer N, Zamanian-Azodi M, Mansouri V, Ghassemi-Broumand M, Rezaei-Tavirani M, Heidari MH, Tavirani MR. Oral squamous cell cancer protein-protein interaction network interpretation in comparison to esophageal adenocarcinoma. Gastroenterology and hepatology from bed to bench. 2017; 10(2):118.
Mukai S, Oue N, Oshima T, Mukai R, Tatsumoto Y, Sakamoto N, Sentani K, Tanabe K, Egi H, Hinoi T, Ohdan H. Overexpression of transmembrane protein BST2 is associated with poor survival of patients with esophageal, gastric, or colorectal cancer. Annals of surgical oncology. 2017; 24(2):594-602.
Inoue Y, Matsuura S, Yoshimura K, Iwashita Y, Kahyo T, Kawase A, Tanahashi M, Maeda M, Ogawa H, Inui N, Funai K. Characterization of VSIG1 exerting a tumor suppressor function in gastric, lung, and esophageal cancer cells. Cancer Science. 2017; 108(8):1701-1714.