{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:45:31Z","timestamp":1770889531623,"version":"3.50.1"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Small cell carcinoma of the esophagus (SCCE) is a rare form of esophageal cancer, which also belongs to the category of neuroendocrine malignant tumors, with a low incidence but high aggressiveness, and a very poor prognosis for patients. Currently, there is a lack of unique staging and treatment guidelines for SCCE. Therefore, a deeper understanding of the therapeutic targets and the mechanisms underlying its occurrence and development is of great importance for early diagnosis, identification of potential therapeutic agents and improvement of the prognosis for patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Firstly, the dataset of SCCE was downloaded from the GEO database and GEO2R tool was employed for the analysis of differentially expressed genes (DEGs). GO and KEGG analysis of DEGs were carried out by using the Bioinformatics and OmicStudio tools. Then, up- and down-regulated genes were intersected with the oncogenes and the tumor suppressor genes respectively, to obtain the differentially expressed onco\/tumor suppressor genes in SCCE. The STRING database was employed to conduct protein-protein interaction (PPI) analysis of differentially expressed onco\/tumor suppressor genes, the network was further constructed in Cytoscape, and hub genes of the network were obtained through the Cytohubba plugin. In addition, miRDB, miRwalk, Targetscan, OncomiR, starbase, Lncbase were used to predict miRNAs and lncRNAs that regulate hub genes, the ceRNA network was built based on this. Transcription factor-miRNA co-regulatory network was analyzed in the NetworkAnalyst database and embellished in Cytoscape. Finally, drugs that may target hub genes were searched through the DGIdb and ConnectivityMAP, and docking verification was performed using Schrodinger.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 820 genes were upregulated and 716 were downregulated, of these, 54 were identified as oncogenes and 85 as tumor suppressor genes. Seven hub genes were identified from the PPI network, which were <jats:italic>AURKA, BIRC5<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>, <jats:italic>FOXM1<\/jats:italic>, <jats:italic>KLF4<\/jats:italic> and <jats:italic>UBE2C<\/jats:italic>. Furthermore, a total of 38 drugs were searched and filtered in DGIdb and ConnectivityMAP, in the molecular docking results of drugs with hub genes, the docking score of <jats:italic>AURKA<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, and <jats:italic>EZH2<\/jats:italic> with multiple drugs were low (&amp;lt;6). In addition, crizotinib with AURKA, lapatinib with CDK1, rucaparib with EZH2, rucaparib with UBE2C were the lowest energy of all molecular docking results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>AURKA, BIRC5<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>, <jats:italic>FOXM1<\/jats:italic>, <jats:italic>KLF4<\/jats:italic> and <jats:italic>UBE2C<\/jats:italic> are the hub genes of SCCE, among them, <jats:italic>AURKA<\/jats:italic>, <jats:italic>CDK1<\/jats:italic> and <jats:italic>EZH2<\/jats:italic> may be used as targets of multiple drugs. Crizotinib, lapatinib, and rucaparib can act on the above targets to inhibit the progression of SCCE and play a therapeutic role.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbinf.2025.1495052","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:41:59Z","timestamp":1738046519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated bioinformatics analysis to explore potential therapeutic targets and drugs for small cell carcinoma of the esophagus"],"prefix":"10.3389","volume":"5","author":[{"given":"Maofei","family":"Zhu","sequence":"first","affiliation":[]},{"given":"Yueming","family":"Chu","sequence":"additional","affiliation":[]},{"given":"Qiang","family":"Yuan","sequence":"additional","affiliation":[]},{"given":"Junfeng","family":"Li","sequence":"additional","affiliation":[]},{"given":"Silin","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006849.pub3","article-title":"Platinum versus non-platinum chemotherapy regimens for small cell lung cancer","volume":"2015","author":"Amarasena","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1016\/j.ajpath.2011.01.034","article-title":"Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of Ube2c in colorectal carcinoma","volume":"178","author":"Bavi","year":"2011","journal-title":"Am. J. Pathol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.7150\/jca.29483","article-title":"A 10-year population-based study of the differences between necs and carcinomas of the esophagus in terms of clinicopathology and survival","volume":"10","author":"Cai","year":"2019","journal-title":"J. Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"D1227","DOI":"10.1093\/nar\/gkad1040","article-title":"Dgidb 5.0: rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms","volume":"52","author":"Cannon","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/j.1442-2050.2010.01112.x","article-title":"Treatment and prognosis of limited disease primary small cell carcinoma of esophagus","volume":"24","author":"Chen","year":"2011","journal-title":"Dis. Esophagus"},{"key":"B6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/1471-2407-14-222","article-title":"Primary small cell carcinoma of the esophagus: clinicopathological study of 44 cases","volume":"14","author":"Chen","year":"2014","journal-title":"BMC Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0242194","DOI":"10.1371\/journal.pone.0242194","article-title":"Identification of potential target genes and crucial pathways in small cell lung cancer based on bioinformatic strategy and human samples","volume":"15","author":"Chen","year":"2020","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1002\/cncr.22887","article-title":"Extrapulmonary small\u2010cell carcinoma compared with small\u2010cell lung carcinoma","volume":"110","author":"Cicin","year":"2007","journal-title":"Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1111\/dote.12017","article-title":"A retrospective study of different treatments of limited-stage small-cell esophageal carcinoma and associated prognostic factor analysis","volume":"26","author":"Ding","year":"2013","journal-title":"Dis. Esophagus"},{"key":"B10","doi-asserted-by":"publisher","first-page":"5405","DOI":"10.1038\/s41388-020-1369-2","article-title":"Sdcbp\/Mda-9\/Syntenin phosphorylation by aurka promotes esophageal squamous cell carcinoma progression through the egfr-pi3k-akt signaling pathway","volume":"39","author":"Du","year":"2020","journal-title":"Oncogene"},{"key":"B11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12943-020-01305-3","article-title":"Targeting aurka in cancer: molecular mechanisms and opportunities for cancer therapy","volume":"20","author":"Du","year":"2021","journal-title":"Mol. Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3892\/or.2023.8553","article-title":"Bioinformatics and experimental validation of an aurka\/tpx2 Axis as a potential target in esophageal squamous cell carcinoma","volume":"49","author":"Du","year":"2023","journal-title":"Oncol. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1021\/acs.jcim.5b00419","article-title":"Homology model-based virtual screening for the identification of human helicase Ddx3 inhibitors","volume":"55","author":"Fazi","year":"2015","journal-title":"J. Chem. Inf. Model"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.semcdb.2005.02.014","article-title":"A roller coaster ride with the mitotic cyclins","volume":"16","author":"Fung","year":"2005","journal-title":"Semin. Cell Dev. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3760\/cma.j.issn.0253-3766.2016.03.004","article-title":"Expression and significance of Foxm1 in esophageal squamous cell carcinoma cells in vitro and in vivo","volume":"38","author":"Gai","year":"2016","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"B17","doi-asserted-by":"publisher","first-page":"12035","DOI":"10.3390\/ijms160612035","article-title":"Dysregulation of Pak1 is associated with DNA damage and is of prognostic importance in primary esophageal small cell carcinoma","volume":"16","author":"Gan","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.ccell.2017.01.006","article-title":"Chemosensitive relapse in small cell lung cancer proceeds through an ezh2-slfn11 Axis","volume":"31","author":"Gardner","year":"2017","journal-title":"Cancer Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-024-03722-y","article-title":"Combining serum Cdk1 with tumor markers for the diagnosis of small cell lung cancer","author":"Han","year":"2024","journal-title":"Clin. Transl. Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1097\/00000478-200503000-00014","article-title":"Cdc2\/Cdk1 expression in esophageal adenocarcinoma and precursor lesions serves as a diagnostic and cancer progression marker and potential novel drug target","volume":"29","author":"Hansel","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"8419","DOI":"10.1038\/ncomms9419","article-title":"Interplay between arginine methylation and ubiquitylation regulates klf4-mediated genome stability and carcinogenesis","volume":"6","author":"Hu","year":"2015","journal-title":"Nat. Commun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/153303461000900301","article-title":"Discovering disease-specific biomarker genes for cancer diagnosis and prognosis","volume":"9","author":"Huang","year":"2010","journal-title":"Technol. Cancer Res. Treat."},{"key":"B23","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/sj.bjc.6603611","article-title":"Small cell oesophageal carcinoma: an institutional experience and review of the literature","volume":"96","author":"Hudson","year":"2007","journal-title":"Br. J. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/modpathol.2016.222","article-title":"Sox2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis","volume":"30","author":"Ishida","year":"2017","journal-title":"Mod. Pathol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1007\/s00535-021-01827-7","article-title":"Jnets clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis","volume":"56","author":"Ito","year":"2021","journal-title":"J. Gastroenterology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1016\/j.molonc.2014.05.012","article-title":"Aurka regulates jak2-stat3 activity in human gastric and esophageal cancers","volume":"8","author":"Katsha","year":"2014","journal-title":"Mol. Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcancer.2023.03.007","article-title":"Foxm1: a small fox that makes more tracks for cancer progression and metastasis","volume":"92","author":"Khan","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1093\/annonc\/mdm476","article-title":"Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the memorial sloan-kettering experience","volume":"19","author":"Ku","year":"2008","journal-title":"Ann. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nrc2044","article-title":"The connectivity map: a new tool for biomedical research","volume":"7","author":"Lamb","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/ncb1217","article-title":"Foxm1 is required for execution of the mitotic programme and chromosome stability","volume":"7","author":"Laoukili","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2894","DOI":"10.1002\/1097-0142(19940615)73:12<2894::Aid-cncr2820731204>3.0.Co;2-m","article-title":"Small cell carcinoma of the esophagus","volume":"73","author":"Law","year":"1994","journal-title":"Cancer"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1111\/jcmm.14882","article-title":"Kr\u00fcppel\u2010like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF\u2010\u03b21\/Smad\/snail pathway","volume":"24","author":"Leng","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/jso.21629","article-title":"A 20\u2010year retrospective study of small\u2010cell carcinomas in taiwan","volume":"102","author":"Li","year":"","journal-title":"J. Surg. Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1136\/jcp.2010.077024","article-title":"Small cell carcinomas in gastrointestinal tract: immunohistochemical and clinicopathological features","volume":"63","author":"Li","year":"","journal-title":"J. Clin. Pathology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1093\/carcin\/bgs143","article-title":"Deficiency of the kruppel-like factor Klf4 correlates with increased cell proliferation and enhanced skin tumorigenesis","volume":"33","author":"Li","year":"2012","journal-title":"Carcinogenesis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.biopha.2017.12.066","article-title":"Ube2c is involved in the functions of Ecrg4 on esophageal squamous cell carcinoma","volume":"98","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1186\/s12885-021-08634-6","article-title":"Overexpression of Ube2c in esophageal squamous cell carcinoma tissues and molecular analysis","volume":"21","author":"Li","year":"","journal-title":"BMC Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1038\/s41467-021-24043-6","article-title":"Multi-omics profiling of primary small cell carcinoma of the esophagus reveals Rb1 disruption and additional molecular subtypes","volume":"12","author":"Li","year":"","journal-title":"Nat. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"101282","DOI":"10.1016\/j.xcrm.2023.101282","article-title":"Aurora a kinase inhibition induces accumulation of sclc tumor cells in mitosis with restored interferon signaling to increase response to Pd-L1","volume":"4","author":"Li","year":"2023","journal-title":"Cell Rep. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4847","DOI":"10.1038\/s41388-021-01895-2","article-title":"Foxm1 is required for small cell lung cancer tumorigenesis and associated with poor clinical prognosis","volume":"40","author":"Liang","year":"2021","journal-title":"Oncogene"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1593\/neo.05832","article-title":"Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2c on esophageal adenocarcinoma","volume":"8","author":"Lin","year":"2006","journal-title":"Neoplasia"},{"key":"B42","doi-asserted-by":"publisher","first-page":"655159","DOI":"10.3389\/fsurg.2021.655159","article-title":"A comparative analysis of the gene expression profiles of small cell esophageal carcinoma, small cell lung cancer, and esophageal adeno\/squamous carcinoma","volume":"8","author":"Liu","year":"2021","journal-title":"Front. Surg."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/3481783","article-title":"Integrated genome-wide analysis of gene expression and DNA copy number variations highlights stem cell-related pathways in small cell esophageal carcinoma","volume":"2018","author":"Liu","year":"2018","journal-title":"Stem Cells Int."},{"key":"B44","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jgg.2016.12.004","article-title":"Ongene: a literature-based database for human oncogenes","volume":"44","author":"Liu","year":"2017","journal-title":"J. Genet. Genomics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s12032-023-02025-6","article-title":"The roles of Ezh2 in cancer and its inhibitors","volume":"40","author":"Liu","year":"2023","journal-title":"Med. Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3892\/or.2014.3194","article-title":"Knocking down the expression of aurora-a gene inhibits cell proliferation and induces G2\/M phase arrest in human small cell lung cancer cells","volume":"32","author":"Lu","year":"2014","journal-title":"Oncol. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1002\/imt2.85","article-title":"Omicstudio: a composable bioinformatics cloud platform with real-time feedback that can generate high-quality graphs for publication","volume":"2","author":"Lyu","year":"2023","journal-title":"Imeta"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e28365","DOI":"10.1016\/j.heliyon.2024.e28365","article-title":"Aurka knockdown inhibits esophageal squamous cell carcinoma progression through ferroptosis","volume":"10","author":"Mi","year":"2024","journal-title":"Heliyon"},{"key":"B49","doi-asserted-by":"publisher","first-page":"936","DOI":"10.5858\/arpa.2013-0119-OA","article-title":"Alterations in the expression of P53, Klf4, and P21 in neuroendocrine lung tumors","volume":"138","author":"Naranjo G\u00f3mez","year":"2014","journal-title":"Arch. Pathol. Lab. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3390\/genes9040188","article-title":"Ube2c is a transcriptional target of the cell cycle regulator Foxm1","volume":"9","author":"Nicolau-Neto","year":"2018","journal-title":"Genes (Basel)"},{"key":"B51","first-page":"719","article-title":"Microrna profiles to predict postoperative prognosis in patients with small cell carcinoma of the esophagus","volume":"35","author":"Okumura","year":"2015","journal-title":"Anticancer Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1096\/fasebj.11.13.9367342","article-title":"Cell cycle regulation by the ubiquitin pathway","volume":"11","author":"Pagano","year":"1997","journal-title":"Faseb J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"65876","DOI":"10.18632\/oncotarget.11674","article-title":"Ube2c is overexpressed in escc tissues and its abrogation attenuates the malignant phenotype of escc cell lines","volume":"7","author":"Palumbo","year":"2016","journal-title":"Oncotarget"},{"key":"B54","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.gde.2016.03.013","article-title":"Emerging roles for polycomb proteins in cancer","volume":"36","author":"Pasini","year":"2016","journal-title":"Curr. Opin. Genet. Dev."},{"key":"B55","doi-asserted-by":"publisher","first-page":"bbae466","DOI":"10.1093\/bib\/bbae466","article-title":"Novel systems biology experimental pipeline reveals matairesinol's antimetastatic potential in prostate cancer: an integrated approach of network pharmacology, bioinformatics, and experimental validation","volume":"25","author":"Rajadnya","year":"2024","journal-title":"Brief. Bioinform"},{"key":"B56","doi-asserted-by":"publisher","first-page":"157","DOI":"10.6026\/97320630010157","article-title":"Pharmacophore and virtual screening of Jak3 inhibitors","volume":"10","author":"Rajeswari","year":"2014","journal-title":"Bioinformation"},{"key":"B57","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mrfmmm.2008.07.010","article-title":"Roles of the Ezh2 histone methyltransferase in cancer epigenetics","volume":"647","author":"Simon","year":"2008","journal-title":"Mutat. Res."},{"key":"B58","first-page":"303","article-title":"Treatment and prognosis of primary esophageal small cell carcinoma","volume":"28","author":"Song","year":"2009","journal-title":"Ai Zheng"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e0294236","DOI":"10.1371\/journal.pone.0294236","article-title":"Srplot: a free online platform for data visualization and graphing","volume":"18","author":"Tang","year":"2023","journal-title":"PLoS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"Gepia: a web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1159\/000432398","article-title":"An old flame never dies: survivin in cancer and cellular senescence","volume":"62","author":"Unruhe","year":"2016","journal-title":"Gerontology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/j.1442-2050.2010.01133.x","article-title":"Small cell carcinoma of the esophagus: a multicentre rare cancer network study","volume":"24","author":"Vos","year":"2011","journal-title":"Dis. Esophagus"},{"key":"B63","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/s41422-018-0039-1","article-title":"The genomic landscape of small cell carcinoma of the esophagus","volume":"28","author":"Wang","year":"2018","journal-title":"Cell Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41698-023-00407-7","article-title":"Targeting Cdk1 in cancer: mechanisms and implications","volume":"7","author":"Wang","year":"2023","journal-title":"NPJ Precis. Oncol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/carcin\/bgi243","article-title":"Emerging role of Klf4 in human gastrointestinal cancer","volume":"27","author":"Wei","year":"2006","journal-title":"Carcinogenesis"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1002\/cam4.2001","article-title":"Primary small cell carcinoma of the esophagus: comparison between a Chinese cohort and surveillance, epidemiology, and end results (seer) data","volume":"8","author":"Xiao","year":"2019","journal-title":"Cancer Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1111\/dote.12230","article-title":"Role of surgery in the management and prognosis of limited-stage small cell carcinoma of the esophagus","volume":"28","author":"Xie","year":"2015","journal-title":"Dis. Esophagus"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.3892\/or.2017.5405","article-title":"Microrna-30d inhibits the migration and invasion of human esophageal squamous cell carcinoma cells via the post-transcriptional regulation of enhancer of zeste homolog 2","volume":"37","author":"Xie","year":"2017","journal-title":"Oncol. Rep."},{"key":"B69","doi-asserted-by":"publisher","first-page":"345","DOI":"10.3892\/ijo.2010.868","article-title":"Aberrant expression of Ezh2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus","volume":"38","author":"Yamada","year":"2011","journal-title":"Int. J. Oncol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"888","DOI":"10.21037\/atm-22-3496","article-title":"Bioinformatics analysis of Birc5 in human cancers","volume":"10","author":"Ye","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"7604","DOI":"10.1038\/s41598-024-58454-4","article-title":"Exploring effective biomarkers and potential immune related gene in small cell lung cancer","volume":"14","author":"Yunchu","year":"2024","journal-title":"Sci. Rep."},{"key":"B72","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1093\/jrr\/rraa052","article-title":"Htert promoter methylation promotes small cell lung cancer progression and radiotherapy resistance","volume":"61","author":"Zhai","year":"2020","journal-title":"J. Radiat. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1515\/bc.2009.060","article-title":"Kr\u00fcppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines","volume":"390","author":"Zhang","year":"2009","journal-title":"Biol. Chem."},{"key":"B74","first-page":"1200","article-title":"Clinical analysis of 22 cases with esophageal primary small cell neuroendocrine carcinoma","volume":"26","author":"Zhang","year":"2019","journal-title":"Chin. J. cancer Prev. Treat."},{"key":"B75","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2407-14-19","article-title":"High-incidence of pten mutations in Chinese patients with primary small cell carcinoma of the esophagus","volume":"14","author":"Zhang","year":"2014","journal-title":"BMC Cancer"},{"key":"B76","doi-asserted-by":"publisher","first-page":"608404","DOI":"10.3389\/fmolb.2020.608404","article-title":"Cd155 overexpression correlates with poor prognosis in primary small cell carcinoma of the esophagus","volume":"7","author":"Zhao","year":"","journal-title":"Front. Mol. Biosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"D1023","DOI":"10.1093\/nar\/gkv1268","article-title":"Tsgene 2.0: an updated literature-based knowledgebase for tumor suppressor genes","volume":"44","author":"Zhao","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"e1173","DOI":"10.1002\/cti2.1173","article-title":"Systematic analysis of the transcriptome in small-cell carcinoma of the oesophagus reveals its immune microenvironment","volume":"9","author":"Zhao","year":"","journal-title":"Clin. Transl. Immunol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"W234","DOI":"10.1093\/nar\/gkz240","article-title":"Networkanalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis","volume":"47","author":"Zhou","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1186\/s12885-020-07416-w","article-title":"Profiles of autophagy-related genes in esophageal adenocarcinoma","volume":"20","author":"Zhu","year":"2020","journal-title":"BMC Cancer"},{"key":"B81","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/dote.12069","article-title":"Primary small cell carcinoma of the esophagus: review of 64 cases from a single institution","volume":"27","author":"Zhu","year":"2014","journal-title":"Dis. Esophagus"},{"key":"B82","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41419-024-06488-x","article-title":"Epigenomic analyses identify Foxm1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma","volume":"15","author":"Ziman","year":"2024","journal-title":"Cell Death Dis."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1495052\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:42:04Z","timestamp":1738046524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1495052\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":82,"alternative-id":["10.3389\/fbinf.2025.1495052"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1495052","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"article-number":"1495052"}}