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The <jats:italic>ABC<\/jats:italic> transporter gene family contributes majorly to cancer chemoresistance. However, effects of somatic expression of most <jats:italic>ABC<\/jats:italic> transporters on cancer outcomes remain largely unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We systematically analyzed expression signatures of all 48 human <jats:italic>ABC<\/jats:italic> transporters in samples from 8562 patients across 14 different cancer types. The association between <jats:italic>CFTR<\/jats:italic> (<jats:italic>ABCC7<\/jats:italic>) expression and outcomes was analyzed experimentally using knock-downs and pharmacological CFTR stimulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Across 720 analyzed clinical associations with patient outcomes, 363 were nominally significant of which 29 remained significant after stringent Bonferroni correction. Among those were various previously known associations, as well as a multitude of novel factors that correlated with poor prognosis or predicted improved outcomes. The association between low <jats:italic>CFTR<\/jats:italic> levels and reduced survival in lung adenocarcinoma was confirmed in two independent cohorts of 246 patients with a history of smoking (logrank <jats:italic>P<\/jats:italic>\u2009=\u20090.0021, hazard ratio [HR], 0.49) and 143 never-smokers (logrank <jats:italic>P<\/jats:italic>\u2009=\u20090.0023, HR 0.31). Further in vitro experiments using naturally <jats:italic>CFTR<\/jats:italic> expressing lung adenocarcinoma cells showed that treatment with CFTR potentiators significantly reduced proliferation at therapeutically relevant concentrations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results suggest that CFTR acts as a pharmacologically activatable tumor suppressor and constitutes a promising target for adjuvant therapy in lung adenocarcinoma.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04106-x","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T19:05:26Z","timestamp":1655492726000},"page":"3293-3302","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CFTR reduces the proliferation of lung adenocarcinoma and is a strong predictor of survival in both smokers and non-smokers"],"prefix":"10.1007","volume":"148","author":[{"given":"Qingyang","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Koutsilieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina-Christina","family":"Sismanoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-6204","authenticated-orcid":false,"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"4106_CR1","first-page":"383","volume":"8","author":"VH Bramwell","year":"2002","unstructured":"Bramwell VH, Morris D, Scott Ernst D, Hings I, Blackstein M, Venner PM, Ette EI, Harding MW, Waxman A, Demetri GD (2002) Safety and efficacy of the multidrug-resistance inhibitor biricodar (VX-710) with concurrent doxorubicin in patients with anthracycline-resistant advanced soft tissue sarcoma. 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The other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The analyzed data is available for aggregate, deidentified analysis and, thus, IRB approval specific to this study was not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}