Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Cancer Research UK Cambridge Cancer Centre, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Sci Rep. 2017 Jul 17;7(1):5554. doi: 10.1038/s41598-017-05623-3.
Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing. MutDNA was detected in 35.3%, 47.1% and 52.9% of pre-NAC plasma, UCP and USN samples respectively, and urine samples contained higher levels of mutDNA (p = <0.001). Longitudinal mutDNA demonstrated tumour evolution under the selective pressure of NAC e.g. in one case, urine analysis tracked two distinct clones with contrasting treatment sensitivity. Of note, persistence of mutDNA detection during NAC predicted disease recurrence (p = 0.003), emphasising its potential as an early biomarker for chemotherapy response.
肌层浸润性膀胱癌 (MIBC) 预后不良。虽然新辅助化疗 (NAC) 可使总体生存率提高 6%，但许多患者对此无反应。体液突变 DNA (mutDNA) 可能允许非侵入性地识别治疗失败。我们从 17 名接受 NAC 的患者中收集了 248 个液体活检样本，包括血浆、细胞沉淀 (UCP) 和上清液 (USN)。我们使用标记扩增子和浅层全基因组测序评估 mutDNA 的单核苷酸变异和拷贝数改变。在接受 NAC 前的血浆、UCP 和 USN 样本中，mutDNA 的检出率分别为 35.3%、47.1%和 52.9%，尿液样本中 mutDNA 水平更高 (p<0.001)。纵向 mutDNA 显示了肿瘤在 NAC 的选择压力下的进化，例如在一个病例中，尿液分析追踪到两个具有不同治疗敏感性的克隆。值得注意的是，NAC 期间 mutDNA 检测的持续存在预测疾病复发 (p=0.003)，强调了其作为化疗反应早期生物标志物的潜力。
