|
|
|
| Identification of biomarkers for esophageal squamous cell carcinoma based on bioinformatics |
| ZHANG Yujun1, WANG Yan2, Diliyaer Wusimanjiang1, LIU Guangchao1, NIE Yanwu1, ZHU Lin2
|
1. School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830054, China;
2. Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China |
|
|
|
|
Abstract Objective To identify biomarkers for esophageal squamous cell carcinoma (ESCC) using bioinformatics tools, so as to provide insights into diagnosis and targeted therapy of ESCC. Methods The gene expression datasets GSE23400, GSE45670, GSE20347 and GSE17351 were screened and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of ESCC were screened using the online tool GEO2R, and the common DEGs among the four datasets were determined using Venn diagram. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database, and protein-protein interaction (PPI) analysis was performed using the STRING database. The key modules were identified using molecular complex detection (MCODE) plugin in the Cytoscape software, and hub genes with the highest connectivity degree were identified using the CytoHubba plugin, and the gene expression was validated on the UALCAN platform. Survival analysis of hub genes was performed using the Kaplan-Meier plotter database. Results Totally 146 common DEGs were screened, including 102 up-regulated genes and 44 down-regulated genes. GO annotation analysis showed that the common DEGs were mainly enriched in biological processes of cell cycle, sister chromatid separation in the late mitotic phase and cell cycle regulation, enriched in cellular components of spindle and centrosome, and molecular functions of enzyme binding and ATP binding. KEGG pathway analysis showed that DEGs was significantly enriched in cell cycle, extracellular matrix (ECM)-receptor interactions and oocyte meiosis. A total of 10 hub genes were screened, and gene expression validation and survival analysis identified 7 genes associated with prognosis of ESCC, including CCNB1, CDK1, BUB1B, ZWINT, AURKA, MAD2L1 and MCM4, which were all highly expressed in ESCC specimens. Conclusion Seven hub genes of ESCC are identified based on bioinformatics, which may serve as biomarkers and therapeutic targets for ESCC.
|
|
Received: 24 March 2022
Revised: 25 June 2022
Published: 08 September 2022
|
|
|
|
|
|
[1] SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2] 杨亮,毛晓锋,邓静,等.2011—2019年长寿区居民食管癌死亡率及早死疾病负担趋势分析[J].预防医学,2021,33(5):500-503.
YANG L,MAO X F,DENG J,et al.Trend analysis of mortality and death burden of esophageal cancer from 2011 to 2019 Changshou District[J].Prev Med,2021,33(5):500-503.
[3] 倪建晓,吴文秀,苏依所,等.2013—2020年瓯海区居民恶性肿瘤死亡趋势及减寿分析[J].预防医学,2022,34(4):413-418.
NI J X,WU W X,SU Y S,et al.Trends in mortality and life lost due to cancer in Ouhai District from 2013 to 2020[J].Prev Med,2022,34(4):413-418.
[4] 满君,张晓梅,宋龙飞.食管鳞状细胞癌差异表达基因的生物信息学分析[J].现代肿瘤医学,2020,28(12):2031-2038.
MAN J,ZHANG X M,SONG L F.Bioinformatics analysis of differentially expressed genes in esophageal squamous cell carcinoma[J]. Mod Oncol,2020,28(12):2031-2038.
[5] 邱洁萍,孙梦雨,左瑞东,等.基于GEO数据库的胃癌差异表达基因的生物信息学分析[J].中国免疫学杂志,2020,36(19):2394-2399.
QIU J P,SUN M Y,ZUO R D,et al.Bioinformatics analysis of differentially expressed genes in gastric cancer based on GEO database[J].China J Immunol,2020,36(19):2394-2399.
[6] 谢长利,李祖茂.基于GEO数据库与生物信息学方法分析食管鳞状细胞癌中的核心基因[J].胃肠病学和肝病学杂志,2021,30(9):1012-1023.
XIE C L,LI Z M.Analysis of key genes in esophageal squamous cell carcinoma based on GEO database and bioinformatics method[J].Chin J Gastroenterol Hepatol,2021,30(9):1012-1023.
[7] KANEHISA M,GOTO S.KEGG:Kyoto Encyclopedia of Genes and Genomes[J].Nucleic Acids Res,2000,28:27-30.
[8] AL DULAIMI D.Recent advances in oesophageal diseases[J].Gastroenterol Hepatol Bed Bench,2014,7(3):186-189.
[9] STEWART S A,WEINBERG R A.Telomeres:cancerto human aging[J].Annu Rev Cell Dev Biol,2006,22(1):531-557.
[10] YANG W,ZHAO X,HAN Y,et al.Identification of hub genes and therapeutic drugs in esophageal squamous cell carcinoma based on integrated bioinformatics strategy[J/OL].Cancer Cell Int,2019,19[2022-06-25].https://doi.org/10.1186/s12935-019-0854-6.
[11] FANG L,LIU Q,CUI H,et al.Bioinformatics analysis highlight differentially expressed CCNB1 and PLK1 genes as potential anti-breast cancer drug targets and prognostic markers[J/OL].Genes,2022,13(4)[2022-06-25].https://doi.org/10.3390/genes13040654.
[12] DONG Y,SUI L,WATANABE Y,et al.Clinical relevance of cyclin B1 overexpression in laryngeal squamous cell carcinoma[J].Cancer Lett,2002,177(1):13-19.
[13] BEGNAMI M D,FREGNANI J H,NONOGAKI S,et al.Evaluation of cell cycle protein expression in gastric cancer:cyclin B1 expression and its prognostic implication[J].Hum Pathol,2010,41(8):1120-1127.
[14] SISINNI L,MADDALENA F,CONDELLI V,et al.TRAP1 controls cell cycle G2-M transition through the regulation of CDK1 and MAD2?expression/ubiquitination[J].J Pathol,2017,243(1):123-134.
[15] LEE M,CHO Y,KIM D,et al.Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1[J].Am J Transl Res,2016,8(12):5246-5255.
[16] FU S,JIN L,GONG T,et al.Effect of sinomenine hydrochloride on radiosensitivity of esophageal squamous cell carcinoma cells[J].Oncol Rep,2018,39(4):1601-1608.
[17] HU M,LIU Q,SONG P,et al.Abnormal expression of the mitotic checkpoint protein BubR1 contributes to the anti-microtubule drug resistance of esophageal squamous cell carcinoma cells[J].Oncol Rep,2013,29(1):185-192.
[18] VLEUGEL M,HOEK T A,TROMER E,et al.Dissecting the roles of human BUB1 in the spindle assembly checkpoint[J].J Cell Sci,2015,128(16):2975-2982.
[19] URBANUCCI A,SAHU B,SEPPÄLÄ J,et al.Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer[J].Oncogene,2012,31(17):2153-2163.
[20] GOLDENSON B,CRISPINO J D.The aurora kinases in cell cycle and leukemia[J].Oncogene,2015,34(5):537-545.
[21] ZHONG X.Identification of crucial miRNAs and genes in esophageal squamous cell carcinoma by miRNA-mRNA integrated analysis[J/OL].Medicine,2019,98(27)[2022-06-25].http://doi.org/10.1097/MD.0000000000016269.
[22] KIKUCHI J,KINOSHITA I,SHIMIZU Y,et al.Minichromosome maintenance(MCM)protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer[J].Lung Cancer,2011,72(2):229-237. |
|
|
|
