{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:35:13Z","timestamp":1782488113887,"version":"3.54.5"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xiaosheng Wang","award":["3150120001"],"award-info":[{"award-number":["3150120001"]}]},{"name":"Linjun You","award":["3150120001"],"award-info":[{"award-number":["3150120001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored. Methods: We hierarchically clustered ACC based on the enrichment levels of twenty-three immune signatures to identify its immune-specific subtypes. Furthermore, we comprehensively compared the clinical and molecular profiles between the subtypes. Results: We identified two immune-specific subtypes of ACC: Immunity-H and Immunity-L, which had high and low immune signature scores, respectively. We demonstrated that this subtyping method was stable and reproducible by analyzing five different ACC cohorts. Compared with Immunity-H, Immunity-L had lower levels of immune cell infiltration, worse overall and disease-free survival prognosis, and higher tumor stemness, genomic instability, proliferation potential, and intratumor heterogeneity. Furthermore, the ACC driver gene CTNNB1 was more frequently mutated in Immunity-L than in Immunity-H. Several proteins, such as mTOR, ERCC1, Akt, ACC1, Cyclin_E1, \u03b2-catenin, FASN, and GAPDH, were more highly expressed in Immunity-L than in Immunity-H. In contrast, p53, Syk, Lck, PREX1, and MAPK were more highly expressed in Immunity-H. Pathway and gene ontology analysis showed that the immune, stromal, and apoptosis pathways were highly enriched in Immunity-H, while the cell cycle, steroid biosynthesis, and DNA damage repair pathways were highly enriched in Immunity-L. Conclusions: ACC can be classified into two stable immune-related subtypes, which have significantly different antitumor responses, molecular characteristics, and clinical outcomes. This subtyping may provide clinical implications for prognostic and immunotherapeutic stratification of ACC.<\/jats:p>","DOI":"10.3390\/biom13010104","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling"],"prefix":"10.3390","volume":"13","author":[{"given":"Qiqi","family":"Lu","sequence":"first","affiliation":[{"name":"Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongfang","family":"Nie","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangti","family":"Luo","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-7093","authenticated-orcid":false,"given":"Xiaosheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjun","family":"You","sequence":"additional","affiliation":[{"name":"Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","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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