Department of Urology, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY.
Department of Healthcare Policy and Research, Weill Cornell Medical Center, New York Presbyterian Hospital, New York, NY.
Urol Oncol. 2021 Jul;39(7):434.e17-434.e22. doi: 10.1016/j.urolonc.2021.01.020. Epub 2021 Feb 6.
Unlike many other cancers, measurement of primary prostate tumor size has no defined role in the management of localized prostate cancer. Here, we assess whether prostate tumor size is associated with aggressive tumor biology using biomarkers of genomic risk.
We abstracted or imputed tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas. We used transcriptomic data to estimate the Cell Cycle Progression Score (CCPS, Prolaris), the Genomic Classifier Score (GCS, Decipher) and the Genomic Prostate Score (GPS, OncotypeDx), SChLaP1 expression, and copy number alteration percentage (%CNA) as well as hallmark gene set enrichment analysis.
Tumor size and gene expression data was available for 267 men. On multivariable regression adjusted for Gleason Grade Group and tumor purity, tumor size was independently associated with the calculated (c)GCS, cGPS, SChLaP1 expression, and %CNA (P< 0.05), but not cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition.
Prostate tumor size is independently associated with established markers of genomic risk. This study nominates the size of a primary prostate cancer as candidate for inclusion in future novel risk scores seeking to quantify cancer aggressiveness.
与许多其他癌症不同,原发性前列腺肿瘤大小的测量在局部前列腺癌的治疗中没有明确的作用。在这里,我们使用基因组风险的生物标志物来评估前列腺肿瘤大小是否与侵袭性肿瘤生物学有关。
我们从纳入癌症基因组图谱的前列腺癌的主要病理学报告中提取或推断肿瘤大小。我们使用转录组数据来估计细胞周期进展评分(CCPS,Prolaris)、基因组分类评分(GCS,Decipher)和基因组前列腺评分(GPS,OncotypeDx)、SChLaP1 表达和拷贝数改变百分比(%CNA)以及标志性基因集富集分析。
有 267 名男性的肿瘤大小和基因表达数据可用。在多变量回归中,根据 Gleason 分级组和肿瘤纯度调整后,肿瘤大小与计算的(c)GCS、cGPS、SChLaP1 表达和%CNA 独立相关(P<0.05),但与 cCCPS 无关。基因集富集分析表明,当调整 Gleason 分级组时,<5 cc 的肿瘤富含雄激素反应基因,而>5 cc 的肿瘤富含 MYC 靶基因和与上皮间质转化相关的基因。
前列腺肿瘤大小与已确立的基因组风险标志物独立相关。这项研究提名原发性前列腺癌的大小作为候选因素,纳入未来寻求量化癌症侵袭性的新风险评分。