Spatial Transcriptomic Profiling to Characterize the Nature of Peripheral- Versus Transition-zone Prostate Cancer.

IF 4.8 2区 医学 Q1 UROLOGY & NEPHROLOGY
Parth Patel, Srinivas Nallandhighal, David Scoville, Brittney Cotta, Zayne Knuth, Daniel Triner, Lynn Tran, Aaron M Udager, Arvind Rao, Todd M Morgan, Ganesh S Palapattu, Vipulkumar Dadhania, Sethu Pitchiaya, Simpa S Salami
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Abstract

Background and objective: Prostate cancer (PC) in the transition zone (TZ) has better prognosis than peripheral-zone (PZ) PC despite higher prostate-specific antigen (PSA) in patients with TZ tumors. Our aim was to characterize molecular differences between TZ and PZ tumors and their clinical implications.

Methods: We performed spatial whole-transcriptome analyses of 50 regions of interest (ROIs) from three patients with PZ and/or TZ PC. ROIs were selected on the basis of SYTO13, pan-cytokeratin, smooth muscle actin, and CD45 markers. Downstream analyses of the transcriptomics data included differential gene expression and Molecular Signatures Database cancer hallmark analysis for pathway enrichment. Survival analyses were performed in The Cancer Genome Atlas (TCGA) prostate data set.

Key findings and limitations: We analyzed Gleason grade 4 (10 ROIs) and grade 5 (10 ROIs) tumors from the PZ, and grade 3 (10 ROIs), grade 4 (11 ROIs), and grade 5 (1 ROI) tumors from the TZ. We observed distinct gene expression profiles between PZ (n = 20) and TZ (n = 22) tumors. TZ ROIs exhibited enrichment of androgen response signaling (ARS; false discovery rate <5%) and a higher androgen subscore of the genomic prostate score (p < 0.001), regardless of grade and the epithelial, stromal, or immune component of the region. Genes underexpressed in PZ tumors, including ARS genes, were associated with poorer progression-free survival in the TCGA data set (n = 451; p < 0.05).

Conclusions and clinical implications: Our results demonstrate higher ARS in TZ tumors than in PZ tumors, explaining the higher PSA and better prognosis for TZ tumors. Further studies are needed to integrate zonal location in diagnostic and treatment algorithms for PC.

Patient summary: We looked at the biological explanation for higher PSA (prostate-specific antigen) levels in blood for cancers found in different zones of the prostate. We found that genes involved in androgen response signaling may explain the higher PSA often seen for tumors in the transition zone than for tumors in the peripheral zone of the prostate. These findings may inform how we diagnose and treat prostate cancer.

空间转录组分析表征外周区与过渡区前列腺癌的性质。
背景与目的:过渡区(TZ)前列腺癌(PC)预后优于外周区(PZ)前列腺癌(PC),尽管TZ肿瘤患者的前列腺特异性抗原(PSA)较高。我们的目的是表征TZ和PZ肿瘤的分子差异及其临床意义。方法:我们对3例PZ和/或TZ PC患者的50个感兴趣区域(roi)进行了空间全转录组分析。根据SYTO13、泛细胞角蛋白、平滑肌肌动蛋白和CD45标记物选择roi。转录组学数据的下游分析包括差异基因表达和分子特征数据库,用于途径富集的癌症标志分析。在癌症基因组图谱(TCGA)前列腺数据集中进行生存分析。主要发现和局限性:我们分析了来自PZ的Gleason 4级(10个ROI)和5级(10个ROI)肿瘤,以及来自TZ的3级(10个ROI), 4级(11个ROI)和5级(1个ROI)肿瘤。我们在PZ (n = 20)和TZ (n = 22)肿瘤中观察到不同的基因表达谱。TZ roi表现出雄激素反应信号(ARS)的富集;结论及临床意义:我们的研究结果表明,TZ肿瘤的ARS高于PZ肿瘤,这解释了TZ肿瘤的PSA较高和预后较好。需要进一步研究将区域定位整合到PC的诊断和治疗算法中。患者总结:我们研究了前列腺不同部位癌症患者血液中PSA(前列腺特异性抗原)水平升高的生物学解释。我们发现,参与雄激素反应信号传导的基因可以解释前列腺过渡区肿瘤的PSA高于前列腺外周区肿瘤的PSA。这些发现可能会告诉我们如何诊断和治疗前列腺癌。
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
European urology focus
European urology focus Medicine-Urology
CiteScore
10.40
自引率
3.70%
发文量
274
审稿时长
23 days
期刊介绍: European Urology Focus is a new sister journal to European Urology and an official publication of the European Association of Urology (EAU). EU Focus will publish original articles, opinion piece editorials and topical reviews on a wide range of urological issues such as oncology, functional urology, reconstructive urology, laparoscopy, robotic surgery, endourology, female urology, andrology, paediatric urology and sexual medicine. The editorial team welcome basic and translational research articles in the field of urological diseases. Authors may be solicited by the Editor directly. All submitted manuscripts will be peer-reviewed by a panel of experts before being considered for publication.
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