{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:50:37Z","timestamp":1787017837027,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013795","name":"Fujian Medical University","doi-asserted-by":"publisher","award":["2017XQ1052"],"award-info":[{"award-number":["2017XQ1052"]}],"id":[{"id":"10.13039\/501100013795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    . Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age\u2010related incidence. Ultrasonography and ultrasonography\u2010guided fine\u2010needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient\u2010oriented and targeted treatment of thyroid nodules and thyroid cancer.\n                    <jats:italic>Methods<\/jats:italic>\n                    . Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein\u2010protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets.\n                    <jats:italic>Results<\/jats:italic>\n                    . We found 219 upregulated and 310 downregulated DEGs, with a cut\u2010off of\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01 and \u2223log\u2009FC | &gt;1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as\n                    <jats:italic>FN1<\/jats:italic>\n                    ,\n                    <jats:italic>APOE<\/jats:italic>\n                    ,\n                    <jats:italic>CLU<\/jats:italic>\n                    , and\n                    <jats:italic>SDC2<\/jats:italic>\n                    . In the targeted regulation network of miRNA\u2010mRNA, the hsa\u2010miR\u2010424\u20105p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    .\n                    <jats:italic>CLU<\/jats:italic>\n                    and\n                    <jats:italic>APOE<\/jats:italic>\n                    are involved in the molecular mechanism of papillary thyroid cancer. The hsa\u2010miR\u2010424\u20105p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.\n                  <\/jats:p>","DOI":"10.1155\/2021\/6752141","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T14:54:11Z","timestamp":1610549651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Comprehensive Identification of Potential Crucial Genes and miRNA\u2010mRNA Regulatory Networks in Papillary Thyroid Cancer"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-8827","authenticated-orcid":false,"given":"Ben-yu","family":"Nan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-4186","authenticated-orcid":false,"given":"Guo-Feng","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-4010","authenticated-orcid":false,"given":"Zi-Rui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-5921","authenticated-orcid":false,"given":"Xi","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3201-4776","authenticated-orcid":false,"given":"Xin-Sheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0263-x"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/965212"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60109-9"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199302253280807"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02162.x"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0110"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000339959"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1054-y"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29038"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-0921-x"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2017.0500"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1158"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.7330"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2016.1161620"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103028"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/1357-2725(95)00027-m"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401779"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209141"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055981"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2004.07.021"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.09.012"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64552-X"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2005.05733.x"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207404"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.223.3.3"},{"key":"e_1_2_10_29_2","first-page":"3276","article-title":"Enhanced radiation sensitivity in prostate cancer by inhibition of the cell survival protein clusterin","volume":"8","author":"Zellweger T.","year":"2002","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-30-113"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.398"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1894"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1016-8478(23)13204-3"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1348-0"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4555"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(83)90047-4"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(91)90138-8"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300418-JLR200"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.044"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283935"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.1.1.507"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605097"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047469"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2012.44.2.121"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-8-31"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1734"},{"key":"e_1_2_10_47_2","first-page":"1313","article-title":"Clinical significance of ApoE expression in human gastric cancer","volume":"20","author":"Sakashita K.","year":"2008","journal-title":"Oncology Reports"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.1.203"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1159\/000107112"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0662-1"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2772-5"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2021\/6752141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2021\/6752141.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/6752141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T02:30:40Z","timestamp":1735612240000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/6752141"}},"subtitle":[],"editor":[{"given":"Monica","family":"Fedele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/6752141"],"URL":"https:\/\/doi.org\/10.1155\/2021\/6752141","archive":["Portico"],"relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"value":"2314-6133","type":"print"},{"value":"2314-6141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6752141"}}