{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:02Z","timestamp":1786969682650,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One of the main causes of lung cancer\u2010related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa_circ_0072309 may be employed as a potential biomarker for BM induced by non\u2010small\u2010cell lung cancer (NSCLC) and to understand its possible underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa_circ_001653, miR\u2010100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription\u2010polymerase chain reaction\n                      <jats:bold>(<\/jats:bold>\n                      qRT\u2010PCR\n                      <jats:bold>)<\/jats:bold>\n                      , and atypical chemokine receptor 3\n                      <jats:bold>(<\/jats:bold>\n                      ACKR3\n                      <jats:bold>)<\/jats:bold>\n                      protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme\u2010linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa_circ_0072309 and its relevant mechanism on BM development, an NSCLC\u2010associated BM model in mice was established.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>According to the results, miR\u2010100 expression was down\u2010regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ_0072309 and ACKR3 expression were up\u2010regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM\u2212 patients. Patients' serum exhibits the same level of hsa_circ_0072309\/miR\u2010100\/ACKR3 expression as in BM samples. Advanced tumor\u2010node\u2010metastasis (TNM) stage, higher BM, shorter post\u2010operative overall survival (OS), and progression\u2010free survival (PFS) are all substantially associated with increased serum circ_0072309 levels in BM+ patients. In animal models, serum owning hsa_circ_0072309 from BM+ patients facilitates BM formation by regulating the miR\u2010100\/ACKR3 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The current preliminary research reveals serum hsa_circ_0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC\u2010derived BM and suggests a substantial role for the hsa_circ_0072309\/miR\u2010100\/ACKR3 axis in the formation of BM from NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.6371","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:34:35Z","timestamp":1690421675000},"page":"18005-18019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Circulating hsa_circ_0072309, acting via the\n                    <scp>miR<\/scp>\n                    \u2010100\/\n                    <scp>ACKR3<\/scp>\n                    pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non\u2010small\u2010cell lung cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiao\u2010Qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of thoracic surgery The Second Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of thoracic surgery The Second Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0132-6219","authenticated-orcid":false,"given":"Lin\u2010Xiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine 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