转录组
DNA甲基化
生物
垂体腺瘤
促肾上腺皮质细胞
人口
甲基化
内科学
癌症研究
生物信息学
腺瘤
内分泌学
垂体
医学
遗传学
基因
基因表达
激素
环境卫生
作者
Rui Milton Patrício da Silva-Júnior,Ana Carolina Bueno,Clarissa Silva Martins,Fernanda Coelli-Lacchini,Jorge Guilherme Okanobo Ozaki,Danillo Cunha de Almeida E Silva,Junier Marrero-Gutiérrez,Antônio Carlos dos Santos,Carlos Garcia-Peral,Hélio Rubens Machado,Marcelo Volpon Santos,Paula Lamparelli Elias,Ayrton Custódio Moreira,Leandro M. Colli,Ricardo Zorzetto Nicoliello Vêncio,Sonir Roberto Rauber Antonini,Margaret de Castro
标识
DOI:10.1210/clinem/dgac703
摘要
To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population.In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo.Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs).This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.
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