Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [⁶⁸Ga]Ga-PSMA-11 PET/CT study.

IF 4.8 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2025-02-25 DOI:10.1186/s13148-025-01811-5

Kilian Kluge, Vincent Lotz, Holger Einspieler, David Haberl, Clemens Spielvogel, Dominik Amereller, Gero Kramer, Bernhard Grubmüller, Shahrokh Shariat, Alexander Haug, Marcus Hacker, Lukas Kenner, Gerda Egger

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引用次数: 0

Abstract

Background: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).

Methods: 122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated.

Results: PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001).

Conclusion: The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.

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前列腺癌中ctDNA甲基化标记物的影像学和预后相关性：一项比较的横截面[⁶⁸Ga]Ga- psma -11 PET/CT研究。

背景：为了验证先前确定的循环肿瘤DNA甲基化标记（甲基- ctdna）面板在疾病检测和生存结果中的临床应用，将甲基- ctdna标记与不同阶段前列腺癌（PCa）男性的PSA水平和PSMA PET/CT结果进行了比较。方法：分析2019年3月至2021年8月期间接受[⁶⁸Ga]Ga- psma -11 PET/CT及血浆取样的122例PCa患者。提取cfDNA，并查询8个单独的甲基- ctdna标记。PET扫描进行定性和定量评估。将PSA和甲基ctdna标记物与PET结果进行比较，并评估其相对预后价值。结果：PSA在所有阴性和肿瘤指示性PET扫描（AUC 0.77）和激素敏感（hsPC）患者（0.737）之间的区分效果最好。在抗去势PCa （CRPC）中，甲基ctdna标记KLF8表现最佳（AUC 0.824）。总的来说，CHST11在非转移扫描和转移扫描之间的区分效果最好（AUC为0.705），KLF8在hsPC和CRPC中最好（AUC为0.662,0.85）。在所有（5/8）和CRPC患者（6/8）中，一些甲基ctdna标记物与肿瘤体积的相关性为低至中等，而PSA水平与所有组的肿瘤体积的相关性为中至强（均p）结论：所研究的甲基ctdna标记物有望用于CRPC的微创检测和预后，但不能用于hsPC的临床表征。前瞻性研究在CRPC的治疗反应和预后预测以及低psa环境下PCa监测的潜在增量价值方面是有必要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.