Department of Biomedical Science, Chosun University, Gwangju 61452, Republic of Korea.
AI Convergence College, Chosun University, Gwangju 61452, Republic of Korea.
Medicina (Kaunas). 2024 Jul 19;60(7):1175. doi: 10.3390/medicina60071175.
Bladder cancer prognosis remains a pressing clinical challenge, necessitating the identification of novel biomarkers for precise survival prediction and improved quality of life outcomes. This study proposes a comprehensive strategy to uncover key prognostic biomarkers in bladder cancer using DNA methylation analysis and extreme survival pattern observations in matched pairs of cancer and adjacent normal cells. Unlike traditional approaches that overlook cancer heterogeneity by analyzing entire samples, our methodology leverages patient-matched samples to account for this variability. Specifically, DNA methylation profiles from adjacent normal bladder tissue and bladder cancer tissue collected from the same individuals were analyzed to pinpoint critical methylation changes specific to cancer cells while mitigating confounding effects from individual genetic differences. Utilizing differential threshold settings for methylation levels within cancer-associated pathways enabled the identification of biomarkers that significantly impact patient survival. Our analysis identified distinct survival patterns associated with specific CpG sites, underscoring these sites' pivotal roles in bladder cancer outcomes. By hypothesizing and testing the influence of methylation levels on survival, we pinpointed CpG biomarkers that profoundly affect the prognosis. Notably, CpG markers, such as cg16269144 (PRKCZ), cg16624272 (PTK2), cg11304234, and cg26534425 (IL18), exhibited critical methylation thresholds that correlate with patient mortality. This study emphasizes the importance of tailored approaches to enhancing prognostic accuracy and refining therapeutic strategies for bladder cancer patients. The identified biomarkers pave the way for personalized prognostication and targeted interventions, promising advancements in bladder cancer management and patient care.
膀胱癌的预后仍然是一个紧迫的临床挑战，因此需要确定新的生物标志物，以进行精确的生存预测和改善生活质量。本研究提出了一种综合策略，通过对配对的癌症和相邻正常细胞中的 DNA 甲基化分析和极端生存模式观察，来发现膀胱癌中的关键预后生物标志物。与传统方法不同，传统方法通过分析整个样本而忽略了癌症异质性，我们的方法利用患者匹配的样本来解释这种变异性。具体来说，分析了来自同一个体的相邻正常膀胱组织和膀胱癌组织的 DNA 甲基化图谱，以确定特定于癌细胞的关键甲基化变化，同时减轻个体遗传差异的混杂影响。在癌症相关途径内利用甲基化水平的差异阈值设置，可以识别对患者生存有重大影响的生物标志物。我们的分析确定了与特定 CpG 位点相关的不同生存模式，强调了这些位点在膀胱癌结果中的关键作用。通过假设和测试甲基化水平对生存的影响，我们确定了对预后有深远影响的 CpG 生物标志物。值得注意的是，CpG 标志物，如 cg16269144（PRKCZ）、cg16624272（PTK2）、cg11304234 和 cg26534425（IL18），表现出与患者死亡率相关的关键甲基化阈值。这项研究强调了采用个体化方法来提高预后准确性和改进膀胱癌患者治疗策略的重要性。确定的生物标志物为个体化预后和靶向干预铺平了道路，有望在膀胱癌管理和患者护理方面取得进展。
