{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:54:00Z","timestamp":1765007640571,"version":"3.46.0"},"reference-count":21,"publisher":"BMJ","issue":"12","funder":[{"name":"Tongzhou High-level Technique Talents Program","award":["YHLD2018006"],"award-info":[{"award-number":["YHLD2018006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072381"],"award-info":[{"award-number":["82072381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Municipal Science and Technology Project","award":["Z181100001918027","Z191100006619079"],"award-info":[{"award-number":["Z181100001918027","Z191100006619079"]}]},{"name":"Beijing Municipal Administration of Hospitals Incubating Program","award":["PX2022065"],"award-info":[{"award-number":["PX2022065"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2024,7,12]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 (\n                      <jats:italic>SHOX2<\/jats:italic>\n                      ) and prostaglandin E2 receptor EP4 (\n                      <jats:italic>PTGER4<\/jats:italic>\n                      ) genes, along with the serum levels of CYFRA21-1, for differential diganosis of malignant pleural mesothelioma (MPM) from benign reactive mesothelial hyperplasia (RMH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed 48 MPM tissue or pleural effusion cell block specimens and 42 cases with RMH. Real-time quantitative methylation-specific PCR was used to examine the methylation status of\n                      <jats:italic>SHOX2<\/jats:italic>\n                      ,\n                      <jats:italic>PTGER4<\/jats:italic>\n                      , ras association domain family 1 isoform A, septin 9 gene and homeobox gene A9 genes. Additionally, we employed electrochemiluminescence immunoassay to measure nine serum tumour markers commonly used in pan-cancer screening tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The receiver operating curve indicated that\n                      <jats:italic>SHOX2<\/jats:italic>\n                      ,\n                      <jats:italic>PTGER4<\/jats:italic>\n                      gene methylation and serum biomarker CYFRA21-1 exhibited good diagnostic performance in identifying MPM, with area under curves (AUCs) of 0.761, 0.904 and 0.847, respectively. The combination of\n                      <jats:italic>SHOX2<\/jats:italic>\n                      ,\n                      <jats:italic>PTGER4<\/jats:italic>\n                      methylation and CYFRA21-1 yielded an AUC value of 0.972. The diagnostic sensitivity and specificity of this panel in differentiating MPM from RMH were 91.3% (42\/46) and 97.6% (41\/42), respectively. Both tissue and cell block specimens can be used in the diagnostic process. Furthermore, elevated CYFRA21-1 levels were associated with poor prognosis (p&lt;0.05). Hypermethylation level of\n                      <jats:italic>PTGER4<\/jats:italic>\n                      may indicate an unfavourable prognosis of MPM, but the difference was not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The combined detection of\n                      <jats:italic>SHOX2<\/jats:italic>\n                      and\n                      <jats:italic>PTGER4<\/jats:italic>\n                      methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2024-209592","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T13:27:20Z","timestamp":1722000440000},"page":"836-842","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Combined detection of SHOX2 and PTGER4 methylation with serum marker CYFRA21-1 for improved diagnosis of malignant pleural mesothelioma"],"prefix":"10.1136","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2023-3330","authenticated-orcid":false,"given":"Nana","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zichen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fudong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"She","sequence":"additional","affiliation":[{"name":"Shanghai Methyldia Technology Co, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaosha","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Methyldia Technology Co, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-1737","authenticated-orcid":false,"given":"Nanying","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"2025120523492511000_78.12.836.1","first-page":"97","article-title":"Incidence of malignant mesothelioma in Germany 2009\u20132013","volume":"28","author":"Lehnert","year":"2017","journal-title":"Cancer Causes Control"},{"key":"2025120523492511000_78.12.836.2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/1753-6405.12503","article-title":"Patterns in the incidence, mortality and survival of malignant pleural and peritoneal mesothelioma, New South Wales, 1972\u20132009","volume":"40","author":"Soeberg","year":"2016","journal-title":"Aust N Z J Public Health"},{"key":"2025120523492511000_78.12.836.3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00428-021-03031-7","article-title":"Pleural mesothelioma classification update","volume":"478","author":"Beasley","year":"2021","journal-title":"Virchows Arch"},{"key":"2025120523492511000_78.12.836.4","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0063-2016"},{"key":"2025120523492511000_78.12.836.5","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/590148","article-title":"Malignant pleural mesothelioma outcomes in the era of combined platinum and folate antimetabolite chemotherapy","volume":"2015","author":"Saint-Pierre","year":"2015","journal-title":"Lung Cancer Int"},{"key":"2025120523492511000_78.12.836.6","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jtho.2021.12.014","article-title":"The 2021 WHO classification of tumors of the pleura: advances since the 2015 classification","volume":"17","author":"Sauter","year":"2022","journal-title":"J Thorac Oncol"},{"key":"2025120523492511000_78.12.836.7","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0240-SA"},{"key":"2025120523492511000_78.12.836.8","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/pin.12453","article-title":"BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests","volume":"66","author":"Hida","year":"2016","journal-title":"Pathol Int"},{"key":"2025120523492511000_78.12.836.9","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/s41379-022-01081-z","article-title":"Clinical and molecular validation of BAP1, MTAP, P53, and merlin immunohistochemistry in diagnosis of pleural mesothelioma","volume":"35","author":"Chapel","year":"2022","journal-title":"Mod Pathol"},{"key":"2025120523492511000_78.12.836.10","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.21037\/tlcr.2019.11.29","article-title":"Application of immunohistochemistry in diagnosis and management of malignant mesothelioma","volume":"9","author":"Chapel","year":"2020","journal-title":"Transl Lung Cancer Res"},{"key":"2025120523492511000_78.12.836.11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41379-021-00895-7","article-title":"Pleural mesothelioma classification\u2014update and challenges","volume":"35","author":"Dacic","year":"2022","journal-title":"Mod Pathol"},{"key":"2025120523492511000_78.12.836.12","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.186"},{"key":"2025120523492511000_78.12.836.13","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1097\/PAS.0000000000000394","article-title":"BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations","volume":"39","author":"Sheffield","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"2025120523492511000_78.12.836.14","doi-asserted-by":"crossref","DOI":"10.1186\/s13148-022-01337-0","article-title":"Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer","volume":"14","author":"Li","year":"2022","journal-title":"Clin Epigenetics"},{"key":"2025120523492511000_78.12.836.15","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.jtho.2021.05.015","article-title":"DNA methylation as a diagnostic biomarker for malignant mesothelioma: a systematic review and meta-analysis","volume":"16","author":"Vandenhoeck","year":"2021","journal-title":"J Thorac Oncol"},{"key":"2025120523492511000_78.12.836.16","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.688274","article-title":"Analysis of the prognostic value and gene expression mechanism of SHOX2 in lung adenocarcinoma","volume":"8","author":"Li","year":"2021","journal-title":"Front Mol Biosci"},{"key":"2025120523492511000_78.12.836.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.01.032"},{"key":"2025120523492511000_78.12.836.18","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.jmoldx.2020.04.205","article-title":"Treatment response monitoring in patients with advanced malignancies using cell-free SHOX2 and SEPT9 DNA methylation in blood: an observational prospective study","volume":"22","author":"de Vos","year":"2020","journal-title":"J Mol Diagn"},{"key":"2025120523492511000_78.12.836.19","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2016.1268308","article-title":"Prostaglandin E(2)-mediated adenosinergic effects on CD14(+) cells: self-amplifying immunosuppression in cancer","volume":"6","author":"Al-Taei","year":"2017","journal-title":"Oncoimmunology"},{"key":"2025120523492511000_78.12.836.20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jphs.2015.10.003","article-title":"Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx\/ASK1\/p38 MAPK pathway","volume":"129","author":"Tsuchiya","year":"2015","journal-title":"J Pharmacol Sci"},{"key":"2025120523492511000_78.12.836.21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1968"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp-2024-209592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:49:35Z","timestamp":1765007375000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp-2024-209592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":21,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,11,19]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/jcp-2024-209592"],"URL":"https:\/\/doi.org\/10.1136\/jcp-2024-209592","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"type":"print","value":"0021-9746"},{"type":"electronic","value":"1472-4146"}],"subject":[],"published":{"date-parts":[[2024,7,26]]}}}