Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling

被引:4
|
作者
Lu, Qiqi [1 ,2 ,3 ]
Nie, Rongfang [1 ,2 ,3 ]
Luo, Jiangti [1 ,2 ,3 ]
Wang, Xiaosheng [1 ,2 ,3 ]
You, Linjun [4 ]
机构
[1] China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Biomed Informat Res Lab, Nanjing 211198, Peoples R China
[2] China Pharmaceut Univ, Canc Genom Res Ctr, Sch Basic Med & Clin Pharm, Nanjing 211198, Peoples R China
[3] China Pharmaceut Univ, Big Data Res Inst, Nanjing 211198, Peoples R China
[4] China Pharmaceut Univ, Ctr New Drug Safety Evaluat & Res, Nanjing 211198, Peoples R China
关键词
adrenocortical carcinoma; immunological classification; clustering analysis; steroid hormones; tumor immune microenvironment; PROGNOSTIC VALUE; ANALYSIS REVEALS; DNA-DAMAGE; CANCER; EXPRESSION; TUMORS; CLASSIFICATION; IMMUNOTHERAPY; BLOCKADE; PATHWAY;
D O I
10.3390/biom13010104
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, beta-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.
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页数:17
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