The First People's Hospital of Foshan, Foshan, 528000, Guangdong, China.
Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362002, Fujian, China.
Clin Transl Oncol. 2024 Aug;26(8):1976-1987. doi: 10.1007/s12094-024-03422-7. Epub 2024 May 22.
The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC).
Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates.
In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection.
Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.
循环肿瘤 DNA（ctDNA）技术的出现为连续监测癌症基因组数据提供了一种便捷、非侵入性的手段，有利于癌症的个体化治疗。本研究旨在评估血浆 ctDNA 联合传统组织下一代测序（NGS）在识别结直肠癌（CRC）中可靶向突变和肿瘤突变负荷（TMB）方面的补充益处。
本研究纳入了 76 例 CRC 患者，采集组织和血浆样本进行 NGS。我们评估了 ctDNA 与组织中基因突变状态的一致性，重点关注 KRAS、NRAS、PIK3CA、BRAF 和 ERBB2 等可操作基因。采用逻辑回归分析探讨了与不一致性和阳性突变率相关的变量。
共鉴定出 26 个癌症相关基因。肿瘤组织和血浆样本中最常见的变异分别为 APC（57.9%比 19.7%）、TP53（55.3%比 22.4%）和 KRAS（47.4%比 43.4%）。组织和 ctDNA 在检测可操作基因突变更替方面的总体一致性为 73.53%。值得注意的是，血浆 ctDNA 提高了某些基因和基因池的检测率。与不一致性显著相关的变量包括性别和腹膜转移。TMB 分析显示组织中的检测率高于血浆，但两者结合可提高检测率。
本研究强调了分析组织和血浆在检测 CRC 中可操作突变方面的重要性，血浆 ctDNA 具有附加价值。不一致性与性别和腹膜转移有关，TMB 分析可以从组织和血浆数据的结合中获益。这种方法为 CRC 的个体化治疗提供了有价值的见解。
