{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:20:42Z","timestamp":1760059242503,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Healt","award":["RC-2025-2797531"],"award-info":[{"award-number":["RC-2025-2797531"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prognostic and predictive role of the human equilibrative nucleoside transporter 1 (hENT-1) has emerged in different cancer types, including intrahepatic cholangiocarcinoma (iCCA), but the mechanisms regulating its expression are poorly understood. Here, we investigated the link between p53 status and hENT-1 regulation in 38 iCCA patients and cell line models; the predictive role of p53 status in response to adjuvant gemcitabine was also investigated. A positive association between mutant p53 cells and hENT-1 expression was observed in iCCA tissue samples; furthermore, patients receiving adjuvant gemcitabine and expressing mutant p53 cells &gt; 4% in tumor tissue had a longer disease-free survival (DFS) than patients expressing mutant p53 cells \u2264 4% (median 18.5 vs. 6 months, p = 0.0229). In iCCA cell line models, transient knockdown of mutant p53 resulted in a decrease in hENT-1 mRNA and protein expression; similarly, restoration of wild-type p53 function induced a significant reduction in hENT-1 mRNA and protein expression. Overall, these findings support a role of p53 status in the regulation of hENT-1 expression, suggesting an opposite effect (activating versus repressive) of mutant and wild-type p53 protein. Furthermore, although the present study should be considered as preliminary, our findings suggest a predictive role of p53 status in iCCA patients treated with gemcitabine, thus deserving future investigations in additional cohorts of cancer patients.<\/jats:p>","DOI":"10.3390\/ijms26115259","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:14:27Z","timestamp":1748585667000},"page":"5259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutant p53 Associates with Human Equilibrative Nucleoside 1 Upregulation and Better Response to Adjuvant Gemcitabine in Intrahepatic Cholangiocarcinoma Patients"],"prefix":"10.3390","volume":"26","author":[{"given":"Marzia","family":"Deserti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Relli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1260-2765","authenticated-orcid":false,"given":"Andrea","family":"Palloni","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Vasuri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"},{"name":"Pathology Unit, Santa Maria delle Croci Ravenna Hospital, 48121 Ravenna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-3675","authenticated-orcid":false,"given":"Deborah","family":"Malvi","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7835-8338","authenticated-orcid":false,"given":"Alessio","family":"Degiovanni","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6591-0193","authenticated-orcid":false,"given":"Simone","family":"Rimedio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-475X","authenticated-orcid":false,"given":"Chiara","family":"Delbaldo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Deiana","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Brandi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"},{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-9698","authenticated-orcid":false,"given":"Simona","family":"Tavolari","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00268-016-3787-4","article-title":"Clinicopathological Features and Post-resection Prognosis of Double Primary Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma","volume":"41","author":"Jung","year":"2017","journal-title":"World J. 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