Background: Metastatic prostate cancer (mPCA) poses challenges in treatment response assessment, particularly in cases where prostate-specific antigen (PSA) levels do not reliably indicate a response. Liquid biopsy, focusing on circulating cell-free DNA (ccfDNA) methylation analysis as a proxy for circulating tumor DNA, offers a non-invasive and cost-effective approach. This study explores the potential of two methylation markers, short stature homeobox 2 (SHOX2) and Septin 9 (SEPT9), as on-mPCA-treatment biomarkers. Methods: Plasma samples were collected from 11 mPCA patients undergoing various treatments. Quantitative assessment of hypermethylated SHOX2 (mSHOX2) and SEPT9 (mSEPT9) levels in ccfDNA was conducted through methylation-specific real-time PCR. Early and overall dynamics of PSA, mSHOX2, and mSEPT9 were analyzed. Statistical evaluation employed Wilcoxon tests. Results: mSHOX2 demonstrated a significant decline post-treatment in patients with a radiographic treatment response as well as in an early treatment setting. mSEPT9 and PSA exhibited non-significant declines. In individual cases, biomarker dynamics revealed unique patterns compared to PSA. Discussion: mSHOX2 and mSEPT9 exhibit dynamics on mPCA treatment. This proof-of-concept study lays the groundwork for further investigation into these markers as valuable additions to treatment response monitoring in mPCA. Further validation in larger cohorts is essential for establishing clinical utility.
背景：转移性前列腺癌（mPCA）的治疗反应评估面临挑战，尤其是在前列腺特异性抗原（PSA）水平无法可靠指示治疗反应的情况下。液体活检以循环游离DNA（ccfDNA）甲基化分析作为循环肿瘤DNA的替代指标，提供了一种非侵入性且经济高效的方法。本研究探讨了两种甲基化标志物——矮小同源盒基因2（SHOX2）和Septin 9（SEPT9）作为mPCA治疗过程中生物标志物的潜力。方法：收集了11例接受不同治疗的mPCA患者的血浆样本。通过甲基化特异性实时荧光定量PCR对ccfDNA中高甲基化的SHOX2（mSHOX2）和SEPT9（mSEPT9）水平进行定量评估。分析了PSA、mSHOX2和mSEPT9的早期及整体动态变化。统计评估采用Wilcoxon检验。结果：在影像学治疗反应良好以及早期治疗阶段，mSHOX2水平在治疗后均呈现显著下降。mSEPT9和PSA的下降趋势则无统计学意义。在个别病例中，生物标志物的动态变化显示出与PSA不同的独特模式。讨论：mSHOX2和mSEPT9在mPCA治疗过程中表现出动态变化特征。这项概念验证研究为进一步探索这些标志物作为mPCA治疗反应监测的重要补充奠定了基础。未来需要在更大规模队列中进行验证，以确立其临床应用价值。
肿瘤(癌症)患者之家