基于 MRI 靶向穿刺和高风险前列腺癌根治术患者手术标本的转录组全分析:靶向必须命中。
Transcriptome Wide Analysis of Magnetic Resonance Imaging-targeted Biopsy and Matching Surgical Specimens from High-risk Prostate Cancer Patients Treated with Radical Prostatectomy: The Target Must Be Hit.
机构信息
Department of Urology, University Hospital Heidelberg, Germany; Department of Radiology, German Cancer Research Center, Heidelberg, Germany.
Research and Development, GenomeDx Biosciences Inc., Vancouver, BC, Canada.
出版信息
Eur Urol Focus. 2018 Jul;4(4):540-546. doi: 10.1016/j.euf.2017.01.005. Epub 2017 Jan 26.
BACKGROUND
The most suspicious lesions on multiparametric magnetic resonance imaging (MRI) may be representative of final pathology.
OBJECTIVE
We connect imaging with high-precision spatial annotation of biopsies and genomic cancer signatures to compare the genomic signals of the index lesion and biopsy cores of adjacent and far away locations.
DESIGN, SETTING, AND PARTICIPANTS: Eleven patients diagnosed with high-risk prostate cancer on MRI/transrectal ultrasound-fusion biopsy (Bx) and treated with radical prostatectomy (RP). Five tissue specimens were collected from each patient.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Whole transcriptome RNA-expression was profiled for each sample. Genomic signatures were used to compare signals in MRI invisible versus visible foci using Pearson's correlation and to assess intratumoral heterogeneity using hierarchical clustering.
RESULTS AND LIMITATIONS
Ten RP and 27 Bx-samples passed quality control. Gene expression between RP and index Bx, but not adjacent benign samples, was highly correlated. Genomic Gleason grade classifier features measured across the different samples showed concordant expression across Bx and RP tumor samples, while an inverse expression pattern was observed between tumor and benign samples indicating the lack of a strong field-effect. The distribution of low and high Prostate Imaging Reporting and Data System (PI-RADS) samples was 10 and 11, respectively. Genomics of all low PI-RADS samples resembled benign tissue and most high PI-RADS samples resembled cancer tissue. A strong association was observed between PI-RADS version 2 and Decipher as well as the genomic Gleason grade classifier score. Clustering analysis showed that most samples cluster tightly by patient. One patient showed unique tumor biology in index versus secondary lesion suggesting the presence of intrapatient heterogeneity and the utility in profiling multiple foci identified by MRI.
CONCLUSIONS
MRI-targeted Bx-genomics show excellent correlation with RP-genomics and confirm the information captured by PI-RADS. Sampling of the target lesion must be precise as correlation between index and benign lesions was not seen.
PATIENT SUMMARY
In this report, we tested if targeted prostate sampling using magnetic resonance imaging-fusion biopsy allows to genetically describe index tumors of prostate cancer. We found that imaging genomics correlated well with final prostatectomy provided that the target is hit precisely.
背景
多参数磁共振成像(MRI)上最可疑的病灶可能代表最终的病理。
目的
我们将影像学与活检的高精度空间标注和癌症基因组特征相结合,比较病灶和远处活检核心的基因组信号。
设计、设置和参与者:11 名患者在 MRI/经直肠超声融合活检(Bx)中被诊断为高危前列腺癌,并接受根治性前列腺切除术(RP)治疗。每位患者采集 5 份组织标本。
结果测量和统计分析
对每个样本进行全转录组 RNA 表达谱分析。使用皮尔逊相关系数比较 MRI 不可见与可见病灶的基因组信号,并使用层次聚类评估肿瘤内异质性。
结果和局限性
10 例 RP 和 27 例 Bx 样本通过质量控制。RP 和指数 Bx 之间的基因表达高度相关,但与相邻良性样本不相关。在不同样本中测量的基因组 Gleason 分级分类器特征在 Bx 和 RP 肿瘤样本中表现出一致的表达,而在肿瘤和良性样本之间观察到相反的表达模式,表明不存在强烈的场效应。低 PI-RADS 和高 PI-RADS 样本的分布分别为 10 例和 11 例。所有低 PI-RADS 样本的基因组学类似于良性组织,大多数高 PI-RADS 样本类似于癌症组织。PI-RADS 版本 2 与 Decipher 以及基因组 Gleason 分级分类器评分之间存在很强的关联。聚类分析表明,大多数样本按患者聚类紧密。一名患者在指数与次要病变中表现出独特的肿瘤生物学,表明存在患者内异质性,并且对 MRI 识别的多个病灶进行分析具有实用性。
结论
MRI 靶向 Bx 基因组学与 RP 基因组学具有很好的相关性,并证实了 PI-RADS 所捕获的信息。由于未观察到指数与良性病变之间的相关性,因此必须精确采样目标病变。
患者总结
在本报告中,我们测试了使用磁共振成像融合活检靶向前列腺采样是否可以从遗传学上描述前列腺癌的指数肿瘤。我们发现,只要准确地定位目标,影像学基因组学与最终的前列腺切除术相关性良好。