Cytology is widely conducted for diagnosis of urotherial bladder cancer, however its sensitivity is still low. Recent studies show that liquid biopsies can reflect tumour genomic profiles. We aim to investigate whether plasma or urine is more suitable for detecting tumour-derived DNA in patients with early stage urotherial bladder cancer. Targeted sequencing of 71 genes was performed using a total of 150 samples including primary tumour, urine supernatant, urine precipitation, plasma and buffy coat from 25 patients with bladder cancer and 5 patients with cystitis and benign tumour. We compared mutation profiles between each sample, identified tumour-identical mutations and compared tumour diagnostic sensitivities between urine and conventional cytology. We identified a total of 168 somatic mutations in primary tumour. In liquid biopsies, tumour-identical mutations were found at 53% (89/168) in urine supernatant, 48% (81/168) in urine precipitation and 2% (3/168) in plasma. The high variant allele fraction of urine was significantly related to worse clinical indicators such as tumour invasion and cytological examination. While conventional cytology detected tumour cells at only 22% of non-invasive tumor, tumour diagnostic sensitivity increased up to 67% and 78% using urine supernatant and precipitation, respectively. Urine is an ideal liquid biopsy for detecting tumour-derived DNA and more precisely reflects tumour mutational profiles than plasma. Genomic analysis of urine is clinically useful for diagnosis of superficial bladder cancer at early stage. This article is protected by copyright. All rights reserved.
Cancer science. 2019 Aug 01 [Epub ahead of print]
Yosuke Hirotsu, Hitoshi Yokoyama, Kenji Amemiya, Takashi Hagimoto, Hironori Daimon, Kyoko Hosaka, Toshio Oyama, Hitoshi Mochizuki, Masao Omata
Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan., Department of Urology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan., Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan., The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.