Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3GE, UK.
School of Medicine, Cedar House, University of Liverpool, Liverpool, L69 3GE, UK.
Br J Cancer. 2022 Jul;127(2):329-336. doi: 10.1038/s41416-022-01785-8. Epub 2022 Mar 29.
The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers.
Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis.
The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-2.8 × 10). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80).
Urinary VOC analysis could aid the diagnosis and surveillance of UBC.
诊断和监测尿路上皮膀胱癌(UBC)需要进行膀胱镜检查。因此,需要寻找生物标志物来降低监测时膀胱镜检查的频率;尿液挥发性有机化合物(VOC)分析可能可以起到这种作用。本横断面研究比较了 UBC 患者和无 UBC 患者的尿液 VOC 谱,以研究代谢组学特征作为生物标志物。
采集血尿门诊接受诊断性膀胱镜检查的患者和接受监测的 UBC 患者的尿液样本。尿液顶空采样采用固相微萃取法,VOC 分析采用气相色谱-质谱法;输出结果进行代谢组学分析。
中位参与者年龄为 70 岁,66.2%为男性。血尿患者中,21 例新诊断为 UBC,125 例无癌症。在监测组中,75 例患者出现复发性 UBC,84 例患者无复发。与对照组相比,UBC 患者的尿液 VOC 谱存在显著差异。有 10 种 VOC 的丰度具有统计学意义,可用于对患者进行分类(错误发现率范围为 1.9×10-2.8×10)。采用内部验证评估了两个预测模型。一个由 8 种 VOC 组成的诊断生物标志物面板获得的 AUROC 为 0.77(灵敏度 0.71,特异性 0.72)。一个由 6 种 VOC 组成的监测生物标志物面板获得的 AUROC 为 0.80(灵敏度 0.71,特异性 0.80)。
尿液 VOC 分析可辅助 UBC 的诊断和监测。