{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:38:31Z","timestamp":1792600711710,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Josephine Nefkens Stichting","award":["JNS-2021-2003"],"award-info":[{"award-number":["JNS-2021-2003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Mitotane is the first-line medical treatment for adrenocortical carcinoma (ACC). Mitotane has substantial drawbacks, including severe toxicity and contralateral gland destruction while effective in only 25%-30% of ACCs. To improve patient selection for mitotane therapy, this study aimed to identify tissue biomarkers associated with in vitro mitotane response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed transcriptomic and proteomic analyses on fresh\u2013frozen human ACC tissues classified as responders (n = 13), partial responders (n = 10), or nonresponders (n = 7) based on in vitro mitotane-induced inhibition of cell proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Responders showed distinct transcriptomic and proteomic signatures compared with partial and nonresponders, whereas fewer differences were found between the latter groups. Integrating transcriptomic and clinicopathological data indicated that responders frequently had cortisol-producing ACC with metastases or nodal involvement. Furthermore, their transcriptomes aligned with aggressive, proliferative ACC subtypes described previously. Differential expression analysis identified 718 genes and 60 proteins that distinguished responders from nonresponders. Pathway and network analyses revealed upregulation of cell cycle and collagen-related genes and downregulation of mitochondria-related genes and proteins in responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, transcriptomic and proteomic profiling offers promise to predict mitotane response in ACC. Our findings suggest that responders exhibit features of aggressive ACC, with distinct molecular characteristics that could serve as biomarkers for treatment selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag168","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:10:48Z","timestamp":1788948648000},"page":"611-624","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic and proteomic signatures predict in vitro response to mitotane in adrenocortical carcinoma"],"prefix":"10.1093","volume":"195","author":[{"given":"Charlotte L","family":"Vi\u00ebtor","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]},{"name":"Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand M","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M","family":"van Koetsveld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid M A","family":"Swagemakers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"van der Spek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M J","family":"Bindels","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lona","family":"Zeneyedpour","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neuro-Oncology, Clinical and Cancer Proteomics, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo M","family":"Luider","sequence":"additional","affiliation":[{"name":"Department of Neurology, Laboratory of Neuro-Oncology, Clinical and Cancer Proteomics, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Louise F","family":"van Velthuysen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-0906","authenticated-orcid":false,"given":"Guillaume","family":"Assi\u00e9","sequence":"additional","affiliation":[{"name":"Genomic and Signaling of Endocrine Tumors, Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM, Institut Cochin , 75014 Paris ,","place":["France"]},{"name":"Department of Endocrinology and National Reference Center for Rare Adrenal Disorders, H\u00f4pital Cochin , 75014 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Jouinot","sequence":"additional","affiliation":[{"name":"Genomic and Signaling of Endocrine Tumors, Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM, Institut Cochin , 75014 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-6209","authenticated-orcid":false,"given":"Johannes","family":"Hofland","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-5165","authenticated-orcid":false,"given":"Wouter W","family":"de Herder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus MC Cancer 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