{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:06:23Z","timestamp":1787893583001,"version":"build-2784847793"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Lung cancer is the leading cause of the global cancer incidence and mortality. It is important to obtain an accurate diagnosis of lymph-node metastasis before surgery to select the therapeutic strategy for non-small cell lung cancer (NSCLC) patients. Carbonic anhydrase 9 (CA9) is considered a marker of hypoxia and it has reported that CA9 is associated with tumor invasion and metastasis. In this study, the correlation between the CA9 expression for lymph-node metastases in NSCLC and [<jats:sup>18<\/jats:sup>F]FDG PET\/CT results was investigated in order to clarify the efficacy of [<jats:sup>18<\/jats:sup>F]FDG PET\/CT for detecting lymph-node metastases of NSCLC patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Among the 564 patients who underwent surgical treatment for NSCLC between 2010 and 2016 at our hospital, a total of 338 patients who underwent preoperative [<jats:sup>18<\/jats:sup>F]FDG PET\/CT were included in this study. CA9 expression was evaluated by immunochemistry. A lymph node with maximum standardized uptake value (SUVmax) \u22652.5 on [<jats:sup>18<\/jats:sup>F]FDG PET\/CT was preoperatively defined as a metastatic lymph node.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Result<\/jats:title>\n<jats:p>CA9 positivity was detected in 122 patients; the other 216 patients were CA9-negative. The CA9-positive NSCLC cases significantly associated with pleural invasion (<jats:italic>p<\/jats:italic> = 0.0063), pT-factor (<jats:italic>p<\/jats:italic> = 0.0080), pN-factor (<jats:italic>p<\/jats:italic> = 0.036) and pStage (<jats:italic>p<\/jats:italic> = 0.043). CA9-positive patients presented significantly poorer survival rate for OS than that of the CA9-negative patients (<jats:italic>p<\/jats:italic> = 0.0024). In the multivariable analysis, histological SCC and CA9 positivity were independent poor-prognosis factors for OS. For the total patient population, the sensitivity and specificity of [<jats:sup>18<\/jats:sup>F]FDG PET\/CT for lymph-node metastases were 54% and 89%, respectively. In contrast, the sensitivity and specificity were particularly low in the CA9-positive SCC cases (36% and 69%, respectively).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>[<jats:sup>18<\/jats:sup>F]FDG PET\/CT might not be useful for diagnosing lymph-node metastases of CA9-positive SCC cases of NSCLC.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0312846","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T17:29:20Z","timestamp":1730222960000},"page":"e0312846","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of CA9 expression in the diagnosis of lymph-node metastases in non-small cell lung cancer based on [18F]FDG PET\/CT"],"prefix":"10.1371","volume":"19","author":[{"given":"Satoshi","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-7228","authenticated-orcid":true,"given":"Masakazu","family":"Yashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Tsukioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kantaro","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Tanimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritoshi","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"issue":"1","key":"pone.0312846.ref001","first-page":"45","article-title":"Epidemiology of lung cancer","volume":"25","author":"KC Thandra","year":"2021","journal-title":"Contemp Oncol (Pozn)"},{"issue":"10","key":"pone.0312846.ref002","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1158\/1055-9965.EPI-19-0221","article-title":"Cancer Progress and Priorities: Lung Cancer","volume":"28","author":"MB Schabath","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"pone.0312846.ref003","doi-asserted-by":"crossref","first-page":"6263249","DOI":"10.1155\/2019\/6263249","article-title":"Preoperative Risk Assessment of Lymph Node Metastasis in cT1 Lung Cancer: A Retrospective Study from Eastern China","volume":"2019","author":"C Zhang","year":"2019","journal-title":"J Immunol Res"},{"issue":"7","key":"pone.0312846.ref004","doi-asserted-by":"crossref","first-page":"e0199970","DOI":"10.1371\/journal.pone.0199970","article-title":"18F-FDG PET intensity correlates with a hypoxic gene signature and other oncogenic abnormalities in operable non-small cell lung cancer","volume":"13","author":"BT Heiden","year":"2018","journal-title":"PLoS One"},{"issue":"3","key":"pone.0312846.ref005","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.suronc.2011.11.001","article-title":"(18)FDG-PET\/CT for detection of mediastinal nodal metastasis in non-small cell lung cancer: a meta-analysis","volume":"21","author":"L Zhao","year":"2012","journal-title":"Surg Oncol"},{"issue":"23","key":"pone.0312846.ref006","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.1158\/1078-0432.CCR-04-0636","article-title":"Carbonic anhydrase IX in early-stage non-small cell lung cancer","volume":"10","author":"SJ Kim","year":"2004","journal-title":"Clin Cancer Res"},{"issue":"2","key":"pone.0312846.ref007","first-page":"149","article-title":"Carbonic anhydrase IX expression correlates with FDG uptake by primary non-small cell lung cancer","volume":"25","author":"G Mees","year":"2010","journal-title":"Cancer Biother Radiopharm"},{"issue":"3215","key":"pone.0312846.ref008","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.124.3215.269","article-title":"On respiratory impairment in cancer cells","volume":"124","author":"O. 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