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We collected clinical and pathological features, genomic mutations, DNA methylation profiles, and mRNA, lncRNA, microRNA, and somatic mutations in ACC patients from the TCGA, GSE19750, GSE33371, and GSE49278 cohorts. Based on the MOVICS algorithm, the patients were divided into ACC1-3 subtypes by comprehensive multi-omics data analysis. We found that immune-related pathways were more activated, and drug metabolism pathways were enriched in ACC1 subtype patients. Furthermore, ACC1 patients were sensitive to PD-1 immunotherapy and had the lowest sensitivity to chemotherapeutic drugs. Patients with the ACC2 subtype had the worst survival prognosis and the highest tumor-mutation rate. Meanwhile, cell-cycle-related pathways, amino-acid-synthesis pathways, and immunosuppressive cells were enriched in ACC2 patients. Steroid and cholesterol biosynthetic pathways were enriched in patients with the ACC3 subtype. DNA-repair-related pathways were enriched in subtypes ACC2 and ACC3. The sensitivity of the ACC2 subtype to cisplatin, doxorubicin, gemcitabine, and etoposide was better than that of the other two subtypes. For 5-fluorouracil, there was no significant difference in sensitivity to paclitaxel between the three groups. A comprehensive analysis of multi-omics data will provide new clues for the prognosis and treatment of patients with ACC.<\/jats:p>","DOI":"10.3390\/cells11233784","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:56:25Z","timestamp":1669611385000},"page":"3784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Cluster Mining of Adrenocortical Carcinoma via Multi-Omics Data Analysis Aids Precise Clinical Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Yu","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affifiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, 81th Meishan Road, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University (AHMU), 81th Meishan Road, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyu","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affifiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, 81th Meishan Road, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University (AHMU), 81th Meishan Road, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-0945","authenticated-orcid":false,"given":"Yiding","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affifiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, 81th Meishan Road, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University (AHMU), 81th Meishan Road, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0728-1047","authenticated-orcid":false,"given":"Yuetian","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxuan","family":"An","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hexi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affifiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, 81th Meishan Road, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University (AHMU), 81th Meishan Road, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affifiliated Hospital of Anhui Medical University, 218th Jixi Road, Hefei 230022, China"},{"name":"Institute of Urology, Anhui Medical University, 81th Meishan Road, Hefei 230022, China"},{"name":"Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University (AHMU), 81th Meishan Road, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cancergen.2012.02.009","article-title":"The molecular basis of adrenocortical cancer","volume":"205","author":"Lehmann","year":"2012","journal-title":"Cancer Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1210\/er.2013-1029","article-title":"Adrenocortical carcinoma","volume":"35","author":"Else","year":"2014","journal-title":"Endocr. 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