Elbialy Abdalla, Sood Akshay, Wang Shang-Jui, Wang Peng, Fadiel Ahmed, Parwani Anil V, Huang Steven, Shvets Gennady, Putluri Nagireddy, Li Jenny, Liu Xuefeng
OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Computational Oncology Unit, The University of Chicago Comprehensive Cancer Center, 900 E 57th Street, KCBD Bldg., STE 4144, Chicago, IL, 60637, USA.
Cell Insight. 2025 Feb 17;4(2):100238. doi: 10.1016/j.cellin.2025.100238. eCollection 2025 Apr.
Prostate cancer exhibits significant racial disparities, with African American (AA) individuals showing ∼64% higher incidence and 2.3 times greater mortality rates compared to their Caucasian (CA) counterparts. Understanding the complex interplay of genetic, environmental, lifestyle, socioeconomic, and healthcare access factors is crucial for developing effective interventions to reduce this disproportionate burden. This study aims to uncover the genetic and transcriptomic differences driving these disparities through a comprehensive analysis using RNA sequencing (RNA-seq) and exome sequencing of prostate cancer tissues from both Black and White patients. Our transcriptomics analysis revealed enhanced activity in pathways linked to immune response and cellular interactions in AA prostate cancer samples, with notable regulation by histone-associated transcription factors (HIST1H1A, HIST1H1D, and HIST1H1B) suggests potential involvement of histone modification mechanisms. Additionally, pseudogenes and long non-coding RNAs (lncRNAs) among the regulated genes indicate non-coding elements' role in these disparities. Exome sequencing identified unique variants in AA patient samples within key genes, including TP73 (tumor suppression), XYLB (metabolism), ALDH4A1 (oxidative stress), PTPRB (cellular signaling), and HLA-DRB5 (immune response). These genetic variations likely contribute to disease progression and therapy response disparities. This study highlights the importance of considering genetic and epigenetic variations in developing tailored therapeutic approaches to improve treatment efficacy and reduce mortality rates across diverse populations.
前列腺癌存在显著的种族差异，与白种人（CA）相比，非裔美国人（AA）的发病率高出约64%，死亡率高出2.3倍。了解遗传、环境、生活方式、社会经济和医疗保健获取因素之间的复杂相互作用，对于制定有效的干预措施以减轻这种不成比例的负担至关重要。本研究旨在通过对黑人和白人患者的前列腺癌组织进行RNA测序（RNA-seq）和外显子组测序的综合分析，揭示导致这些差异的遗传和转录组差异。我们的转录组学分析显示，AA前列腺癌样本中与免疫反应和细胞相互作用相关的通路活性增强，组蛋白相关转录因子（HIST1HIA、HIST1HID和HIST1HIB）的显著调控表明组蛋白修饰机制可能参与其中。此外，受调控基因中的假基因和长链非编码RNA（lncRNA）表明非编码元件在这些差异中发挥作用。外显子组测序在关键基因的AA患者样本中鉴定出独特的变异，包括TP73（肿瘤抑制）、XYLB（代谢）、ALDH4A1（氧化应激）、PTPRB（细胞信号传导）和HLA-DRB5（免疫反应）。这些基因变异可能导致疾病进展和治疗反应差异。本研究强调了在制定个性化治疗方法时考虑遗传和表观遗传变异的重要性，以提高治疗效果并降低不同人群的死亡率。
