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http://dx.doi.org/10.7314/APJCP.2015.16.4.1361

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics  

Wang, Da-Guang (Gastrointestinal surgery, the First Hospital of Jilin University)
Chen, Guang (Vascular surgery, the First Hospital of Jilin University)
Wen, Xiao-Yu (Hepatobiliary and pancreatic, the First Hospital of Jilin University)
Wang, Dan (Gastrointestinal Department of Internal Medicine, the First Hospital of Jilin University)
Cheng, Zhi-Hua (Vascular surgery, the First Hospital of Jilin University)
Sun, Si-Qiao (Vascular surgery, the First Hospital of Jilin University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.4, 2015 , pp. 1361-1365 More about this Journal
Abstract
Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.
Keywords
Gastric cancer; differentially expressed genes; diagnosis; biomarkers;
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1 Begnami MD, Fregnani JHT, Nonogaki S, et al (2010). Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication. Human pathol, 41, 1120-7.   DOI
2 Bolstad BM, Irizarry RA, Astrand M, et al (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics, 19, 185-93.   DOI
3 Bridges JR CC (1966). Hierarchical cluster analysis. Psychol Rep, 18, 851-4.   DOI
4 Carpelan-Holmstrom M, Louhimo J, Stenman U-H, et al (2001). CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers. Anticancer Res, 22, 2311-6.
5 Chow JP, Siu WY, Fung TK, et al (2003). DNA damage during the spindle-assembly checkpoint degrades Cdc25A, inhibits cyclin-cdc2 complexes, and reverses cells to interphase. Mol Biol Cell, 14, 3989-4002.   DOI   ScienceOn
6 Consortium GO (2004). The Gene Ontology (GO) database and informatics resource. Nucleic acids Res, 32, 258-61.   DOI
7 Da Wei Huang BTS, Lempicki RA (2008). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols, 4, 44-57.   DOI
8 Dennis Jr G, Sherman BT, Hosack DA, et al (2003). DAVID: database for annotation, visualization, and integrated discovery. Genome Biol, 4, 3.   DOI
9 Fawcett T (2006). An introduction to ROC analysis. Pattern Recogn Lett, 27, 861-74.   DOI
10 Ford HL, Pardee AB (1999). Cancer and the cell cycle. J Cellular Biochem, 75, 166-72.   DOI
11 Gallant P, Nigg E (1992). Cyclin B2 undergoes cell cycledependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells. J Cell Biol, 117, 213-24.   DOI
12 Garcia AME, Alfaro A, Palma I, et al (2013). Expression of biomarkers in cervical intraepithelial neoplasia: Potential use screening. Mol Cancer Ther, 12, A46.   DOI
13 Gonzalez CA, Sala N, Rokkas T (2013). Gastric cancer: epidemiologic aspects. Helicobacter, 18, 34-8.   DOI
14 Kawamoto H, Koizumi H, Uchikoshi T (1997). Expression of the G2-M checkpoint regulators cyclin B1 and cdc2 in nonmalignant and malignant human breast lesions: immunocytochemical and quantitative image analyses. Am J Pathol, 150, 15.
15 Hofmann H-S, Hansen G, Burdach S, et al (2004). Discrimination of human lung neoplasm from normal lung by two target genes. Am J Resp Crit Care Med, 170, 516-9.   DOI
16 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.   DOI
17 Kanehisa M, Goto S (2000). KEGG: kyoto encyclopedia of genes and genomes. Nucleic acids Res, 28, 27-30.   DOI
18 Kim D-H (2007). Prognostic implications of cyclin B1, p34cdc2, p27Kip1 and p53 expression in gastric cancer. Yonsei Med J, 48, 694-700.   DOI
19 Kim D, Lee H, Nam E, et al (2000). Reduced expression of the cell-cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma. Histopathology, 36, 245-51.   DOI
20 Kushner J, Bradley G, Young B, et al (1999). Aberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma. J Oral Pathol Med, 28, 77-81.
21 Leung WK, Wu M-s, Kakugawa Y, et al (2008). Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol, 9, 279-87.   DOI
22 Li X-K, Motwani M, Tong W, et al (2000). Huanglian, a Chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells. Mol Pharm, 58, 1287-93.   DOI
23 Mashal RD, Lester S, Corless C, et al (1996). Expression of cell cycle-regulated proteins in prostate cancer. Cancer Res, 56, 4159-63.
24 Lin J-P, Yang J-S, Lee J-H, et al (2006). Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line. World J Gastroenterol, 12, 21.   DOI
25 Liu H, Zhu L, Liu B, et al (2012). Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett, 316, 196-203.   DOI   ScienceOn
26 Liu R, Zhang C, Hu Z, et al (2011). A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Euro J Cancer, 47, 784-91.   DOI   ScienceOn
27 Orditura M, Galizia G, Sforza V, et al (2014). Treatment of gastric cancer. World J Gastroenterol, 20, 1635-49.   DOI
28 Otsubo T, Akiyama Y, Yanagihara K, et al (2008). SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. Bri J Cancer, 98, 824-31.   DOI
29 Park S-H, Yu G-R, Kim W-H, et al (2007). NF-Y-dependent cyclin B2 expression in colorectal adenocarcinoma. Clin Cancer Res, 13, 858-67.   DOI
30 Sarafan-Vasseur N, Lamy A, Bourguignon J, et al (2002). Overexpression of B-type cyclins alters chromosomal segregation. Oncogene, 21, 2051-7.   DOI
31 Schwartz GK, Shah MA (2005). Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol, 23, 9408-21.   DOI
32 Smyth GK (2004). Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol.
33 Van Cutsem E, de Haas S, Kang Y-K, et al (2012). Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol, 39, 9824.
34 Suzuki H, Graziano DF, McKolanis J, et al (2005). T Cell dependent antibody responses against aberrantly expressed cyclin B1 protein in patients with cancer and premalignant disease. Clin Cancer Res, 11, 1521-6.   DOI
35 Takahashi Y, Takeuchi T, Sakamoto J, et al (2003). The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study. Gastric Cancer, 6, 142-5.   DOI
36 Takaishi S, Okumura T, Tu S, et al (2009). Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells, 27, 1006-20.   DOI
37 Wang A, Yoshimi N, Ino N, et al (1997). Overexpression of cyclin B1 in human colorectal cancers. J Cancer Res Clin Oncol, 123, 124-7.   DOI
38 Yang L (2006). Incidence and mortality of gastric cancer in China. World J Gastroenterol, 12, 17-20.   DOI
39 Yasuda M, Takesue F, Inutsuka S, et al (2002). Overexpression of cyclin B1 in gastric cancer and its clinicopathological significance: an immunohistological study. J Cancer Res Clin Oncol, 128, 412-6.   DOI
40 Yonemura Y, Ninomiya I, Yamaguchi A, et al (1991). Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res, 51, 1034-8.
41 Yuan J, Kramer A, Matthess Y, et al (2005). Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo. Oncogene, 25, 1753-62.
42 Zhou X-Y, Wang X, Hu B, et al (2002). An ATM-independent S-phase checkpoint response involves CHK1 pathway. Cancer Res, 62, 1598-603.