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And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8\/18\/19) and mesenchymal (vimentin and TWIST1) markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial\/mesenchymal phenotypes (E\/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn\u2019t detect CTCs, the overall CTCs detection rate was 97.5% (80\/82). For 60 treatment na\u00efve NSCLC, only one patient didn\u2019t detect CTCs. The median number of total CTCs, hybrid E\/M phenotype CTCs, E-CTCs and M-CTCs per 5\u00a0mL blood was 22 (range 1\u201390), 13 (range 0\u201383), 1 (range 0\u201317 and 0\u201347), respectively. Hybrid E\/M CTCs, especially the e\u2009=\u2009m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more\u00a0than the numbers observed in early stage patients. Patients with pure hybrid E\/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E\u2009+\u2009E\/M CTCs (20% vs 9%) and E\/M\u2009+\u2009M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E\/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We concluded that E-CTCs with a hybrid E\/M phenotype are associated to metastasis in therapy-na\u00efve NSCLC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-021-03681-9","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T06:24:13Z","timestamp":1626157453000},"page":"1137-1146","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC"],"prefix":"10.1007","volume":"148","author":[{"given":"Yujuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Men","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puyuan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danfei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7189-4692","authenticated-orcid":false,"given":"Zhouguang","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"3681_CR1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3390\/cancers11040483","volume":"11","author":"C Agnoletto","year":"2019","unstructured":"Agnoletto C, Corr\u00e0 F, Minotti L, Baldassari F, Crudele F, Cook WJJ, Di Leva G, d\u2019Adamo AP, Gasparini P, Volinia S (2019) Heterogeneity in circulating tumor cells: the relevance of the stem-cell subset. 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