前列腺癌的表观遗传学分析揭示了潜在的预后特征。
Epigenetic profiling of prostate cancer reveals potential prognostic signatures.
发表日期:2024 Aug 24
作者:
Simon Bernatz, Ian G Reddin, Tim R Fenton, Thomas J Vogl, Peter J Wild, Jens Köllermann, Philipp Mandel, Mike Wenzel, Benedikt Hoeh, Scherwin Mahmoudi, Vitali Koch, Leon D Grünewald, Renate Hammerstingl, Claudia Döring, Patrick N Harter, Katharina J Weber
来源:
Cellular & Molecular Immunology
摘要:
虽然表观遗传分析在几种肿瘤实体中发现了生物标志物,但其在前列腺癌中的应用仍然有限。我们探索了基于 DNA 甲基化的良性和恶性前列腺组织解卷积以发现生物标志物,以及放射组学作为非侵入性替代物的潜力。我们回顾性纳入了 30 名患有前列腺癌 (PCa) 的患者(63 [58-79] 岁),他们患有前列腺癌 (PCa)。 2014 年至 2019 年间,在根治性前列腺切除术之前对前列腺进行多参数 MRI 检查。对照组包括 4 名前列腺癌病变附近有良性前列腺组织的患者和 4 名良性前列腺增生患者。获得所有病变的组织穿孔。进行 DNA 甲基化分析和无参考计算机解卷积以检索潜在甲基化成分 (LCM)。分析基于 LCM 的聚类的细胞组成并与临床疾病参数相关。此外,使用放射组学分析前列腺癌和邻近良性病变,以非侵入性地预测表观遗传特征。LCM 识别出两个具有潜在预后影响的簇。簇一与恶性前列腺组织相关(p<0.001),并且 CD19 和 CD4 细胞的免疫细胞相关特征减少(p=0.004)。簇一仅包含富含显着前列腺癌和晚期肿瘤阶段的恶性前列腺组织(两者的p<0.03)。没有放射组学模型可以非侵入性地预测表观遗传簇。表观遗传簇与前列腺癌的预后和临床相关指标相关。此外,免疫细胞相关特征在预后有利和不利的簇之间存在显着差异。需要进一步研究来探索潜在的诊断和治疗意义。© 2024。作者。
While epigenetic profiling discovered biomarkers in several tumor entities, its application in prostate cancer is still limited. We explored DNA methylation-based deconvolution of benign and malignant prostate tissue for biomarker discovery and the potential of radiomics as a non-invasive surrogate.We retrospectively included 30 patients (63 [58-79] years) with prostate cancer (PCa) who had a multiparametric MRI of the prostate before radical prostatectomy between 2014 and 2019. The control group comprised four patients with benign prostate tissue adjacent to the PCa lesions and four patients with benign prostatic hyperplasia. Tissue punches of all lesions were obtained. DNA methylation analysis and reference-free in silico deconvolution were conducted to retrieve Latent Methylation Components (LCMs). LCM-based clustering was analyzed for cellular composition and correlated with clinical disease parameters. Additionally, PCa and adjacent benign lesions were analyzed using radiomics to predict the epigenetic signatures non-invasively.LCMs identified two clusters with potential prognostic impact. Cluster one was associated with malignant prostate tissue (p < 0.001) and reduced immune-cell-related signatures (p = 0.004) of CD19 and CD4 cells. Cluster one comprised exclusively malignant prostate tissue enriched for significant prostate cancer and advanced tumor stages (p < 0.03 for both). No radiomics model could non-invasively predict the epigenetic clusters.Epigenetic clusters were associated with prognostically and clinically relevant metrics in prostate cancer. Further, immune cell-related signatures differed significantly between prognostically favorable and unfavorable clusters. Further research is necessary to explore potential diagnostic and therapeutic implications.© 2024. The Author(s).