Kim Hongkyung, Park Jee Soo, Choi Zisun, Min Seungki, Park Jihyang, Shin Saeam, Choi Jong Rak, Lee Seung-Tae, Ham Won Sik
Department of Laboratory Medicine, Chung-Ang University Gwangmyung Hospital, Chung-Ang University College of Medicine, Gwangmyung 14353, Republic of Korea.
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea.
Cancers (Basel). 2023 Jun 23;15(13):3306. doi: 10.3390/cancers15133306.
Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.
循环肿瘤DNA（ctDNA）是透明细胞肾细胞癌（ccRCC）一种很有前景的生物标志物；然而，其在ccRCC小肾肿块中的特征仍不清楚。在这项前瞻性研究中，我们探究了pT1a期ccRCC中ctDNA的特征。术前从53例pT1a期ccRCC患者中采集血浆样本。使用下一代测序对pT1a期ccRCC的ctDNA进行分析，并与更高分期的ccRCC进行比较。研究了pT1a期ccRCC中ctDNA与临床病理特征的相关性。评估了ctDNA与匹配组织之间突变的正相关关系。在pT1a期ccRCC中，ctDNA检测率、游离DNA浓度和中位变异等位基因频率分别为20.8%、5.8 ng/mL和0.38%，显著低于转移性ccRCC。pT1a样本中ctDNA基因比例与转移性ccRCC样本不同。未阐明ctDNA与肿瘤大小、肿瘤分级和患者年龄之间的关系。对于pT1a期ccRCC，ctDNA与匹配组织之间的正一致性较差。需要采取策略提高敏感性，同时消除克隆性造血引起的噪音，以提高ctDNA分析在ccRCC小肾肿块中的临床应用价值。
