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多类固醇分析与机器学习揭示雄激素作为子宫内膜癌诊断的候选生物标志物:一项病例对照研究。

Multi-Steroid Profiling and Machine Learning Reveal Androgens as Candidate Biomarkers for Endometrial Cancer Diagnosis: A Case-Control Study.

作者信息

Gjorgoska Marija, Taylor Angela E, Smrkolj Špela, Rižner Tea Lanišnik

机构信息

Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK.

出版信息

Cancers (Basel). 2025 May 16;17(10):1679. doi: 10.3390/cancers17101679.

DOI:10.3390/cancers17101679
PMID:40427176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12110686/
Abstract

OBJECTIVE

To evaluate the diagnostic and prognostic potential of preoperative serum steroid levels in endometrial cancer (EC) alone and in combination with clinical parameters and biomarkers CA-125 and HE4.

METHODS

This single-center observational study included 62 patients with EC and 70 controls with benign uterine conditions who underwent surgery between June 2012 and February 2020. Preoperative serum levels of classic androgens, 11-oxyandrogens, glucocorticoids and mineralocorticoids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Machine learning was used to assess their diagnostic and prognostic value alone and combined with clinical parameters and tumor biomarkers.

RESULTS

Patients with EC had significantly higher serum levels of classic androgens (androstenedione, testosterone), 11-oxyandrogens (11β-hydroxy-androstenedione, 11β-hydroxy-testosterone) and glucocorticoids (17α-hydroxy-progesterone, 11-deoxycortisol) compared to controls. While individual steroids had limited diagnostic value, a multivariate model including classic androgens, CA-125, HE4, BMI and parity achieved an AUC 0.87, 79.1% sensitivity and 74.7% specificity in distinguishing EC from benign uterine condition. This model outperformed our previously published model based on CA-125, HE4 and BMI (AUC: 0.81, < 0.0001). Prognostically, HE4 was the strongest marker for lymphovascular space invasion (LVSI) (AUC: 0.79) and deep myometrial invasion (MI) (AUC: 0.71). Among steroids, androstenedione was the most predictive of LVSI (AUC: 0.67), while 11β-hydroxy-testosterone was the strongest predictor of deep MI (AUC: 0.64).

CONCLUSIONS

Patients with EC exhibit distinct steroid hormone profiles. While steroids alone offer modest diagnostic and prognostic value, integrating them into multivariate models improves diagnostic accuracy.

摘要

目的

评估术前血清类固醇水平单独及联合临床参数和生物标志物CA - 125与HE4在子宫内膜癌(EC)中的诊断和预后潜力。

方法

这项单中心观察性研究纳入了2012年6月至2020年2月期间接受手术的62例EC患者和70例患有良性子宫疾病的对照者。使用液相色谱 - 串联质谱法(LC - MS/MS)测量术前血清中经典雄激素、11 - 氧代雄激素、糖皮质激素和盐皮质激素的水平。采用机器学习评估它们单独及联合临床参数和肿瘤生物标志物的诊断和预后价值。

结果

与对照组相比,EC患者血清中经典雄激素(雄烯二酮、睾酮)、11 - 氧代雄激素(11β - 羟基雄烯二酮、11β - 羟基睾酮)和糖皮质激素(17α - 羟孕酮、11 - 脱氧皮质醇)水平显著更高。虽然单个类固醇的诊断价值有限,但一个包含经典雄激素、CA - 125、HE4、BMI和产次的多变量模型在区分EC与良性子宫疾病时的曲线下面积(AUC)为0.87,灵敏度为79.1%,特异度为74.7%。该模型优于我们之前发表的基于CA - 125、HE4和BMI的模型(AUC:0.81,P < 0.0001)。在预后方面,HE4是淋巴管间隙浸润(LVSI)(AUC:0.79)和子宫肌层深层浸润(MI)(AUC:0.71)的最强标志物。在类固醇中,雄烯二酮对LVSI的预测性最强(AUC:0.67),而11β - 羟基睾酮是子宫肌层深层浸润的最强预测因子(AUC:0.64)。

结论

EC患者表现出独特的类固醇激素谱。虽然单独的类固醇具有一定的诊断和预后价值,但将它们纳入多变量模型可提高诊断准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/7d20bfc5a3b4/cancers-17-01679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/3575848d01bf/cancers-17-01679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/1a21009cb2da/cancers-17-01679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/7d20bfc5a3b4/cancers-17-01679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/3575848d01bf/cancers-17-01679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/1a21009cb2da/cancers-17-01679-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/256c/12110686/7d20bfc5a3b4/cancers-17-01679-g003.jpg

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Gynecol Oncol. 2025 Feb;193:1-11. doi: 10.1016/j.ygyno.2024.12.010. Epub 2024 Dec 30.
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SIR-EN-New Biomarker for Identifying Patients at Risk of Endometrial Carcinoma in Abnormal Uterine Bleeding at Menopause.SIR-EN-用于识别绝经后异常子宫出血中子宫内膜癌风险患者的新型生物标志物。
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Pre-receptor regulation of 11-oxyandrogens differs between normal and cancerous endometrium and across endometrial cancer grades and molecular subtypes.
11-氧代雄烯二酮的受体前调节在正常和癌变子宫内膜以及子宫内膜癌分级和分子亚型之间存在差异。
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Early detection of uterine corpus endometrial carcinoma utilizing plasma cfDNA fragmentomics.利用血浆 cfDNA 片段组学早期检测子宫体子宫内膜癌。
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