In Situ Metabolomics of Cortisol-Producing Adenomas.
In Situ Metabolomics of Cortisol-Producing Adenomas.
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DOI：
10.1093/clinchem/hvac191
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发表时间：
2023-02-01
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
组学技术的最新进展已经允许对产生皮质醇的肾上腺腺瘤（CPA）进行详细的遗传表征。相比之下，cpa的病理生理尚未在肿瘤代谢改变水平上得到详细阐明。目前的研究进行了一个全面的质谱成像（MSI）图的cpa的临床表型和免疫组织化学特征的甾体原酶。该研究队列包括46例肾上腺肿瘤患者，包括cpa （n = 35）和非功能性腺瘤（n = 11）。皮质醇高分泌程度与29种代谢物显著相关（校正P <0.05）。经典雄激素途径产生的肾上腺雄激素与皮质醇分泌（rs = - 0.41，调整P = 0.035）和CYP11B1表达（rs = - 0.77，调整P = 2.00E-08）呈负相关。皮质醇过量程度和肿瘤CYP11B1表达与血清素进一步相关（rs = 0.48和0.62，调整后P = 0.008和2.41E-05）。肿瘤大小与13种脂肪酸丰度相关（校正P <0.05），与磷脂酸38:8等9种多不饱和脂肪酸呈负相关（rs = - 0.56，校正P = 0.009）。MSI揭示了内分泌功能与肿瘤发生之间新的代谢联系，这将进一步支持对CPA病理生理学的理解。
Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations. The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n = 35) and non-functional adenomas (n = 11). Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P <0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs = −0.41, adjusted P = 0.035) and CYP11B1 expression (rs = −0.77, adjusted P = 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs = 0.48 and 0.62, adjusted P = 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P <0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs = −0.56, adjusted P = 0.009). MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.
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影响因子：
8
作者：
Murakami, Masanori;Rhayem, Yara;Beuschlein, Felix
通讯作者：
Beuschlein, Felix
影响因子：
5.8
作者：
Di Dalmazi, Guido;Quinkler, Marcus;Beuschlein, Felix
通讯作者：
Beuschlein, Felix
影响因子：
5.8
作者：
Di Dalmazi, Guido;Fanelli, Flaminia;Pasquali, Renato
通讯作者：
Pasquali, Renato
影响因子：
2.7
作者：
Gomez-Sanchez, Celso E.;Lewis, Mark;Gomez-Sanchez, Elise P.
通讯作者：
Gomez-Sanchez, Elise P.
影响因子：
7.4
作者：
Edwards, JL;Kennedy, RT
通讯作者：
Kennedy, RT