Clinical Genomics Pty Ltd, North Ryde, NSW, Australia.
Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University of South Australia, Bedford Park, SA, 5042, Australia.
J Cancer Res Clin Oncol. 2018 Sep;144(9):1741-1750. doi: 10.1007/s00432-018-2701-x. Epub 2018 Jul 10.
Methylation in IKZF1 and BCAT1 are common events in colorectal cancer (CRC). They are often detected in blood as circulating tumor DNA (ctDNA) at diagnosis and disappear after surgery in most CRC patients. A prospective study was conducted to determine the relationship between detection of these markers following surgery and risk for residual disease and for recurrence.
ctDNA status with methylated BCAT1 and IKZF1 was determined within 12 months of surgical resection of CRC, and was related to presence of or risk for residual disease (margins involved, metastases present or nature of node involvement), and to recurrence-free survival.
Blood was collected from 172 CRC patients after surgery and 28 (16%) were ctDNA positive. Recurrence was diagnosed in 23 of the 138 with clinical follow-up after surgery (median follow-up 23.3 months, IQR 14.3-29.5). Multivariate modeling indicated that features suggestive of residual disease were an independent predictor of post-surgery ctDNA status: cases with any of three features (close resection margins, apical node involved, or distant metastases) were 5.3 times (95% CI 1.5-18.4, p = 0.008) more likely to be ctDNA positive. Multivariate analysis showed that post-surgery ctDNA positivity was independently associated with an increased risk of recurrence (HR 3.8, 1.5-9.5, p = 0.004).
CRC cases positive for methylated ctDNA after surgery are at increased risk of residual disease and subsequently recurrence. This could have implications for guiding recommendations for adjuvant therapy and surveillance strategies. Randomized studies are now indicated to determine if monitoring cases with these biomarkers leads to survival benefit.
IKZF1 和 BCAT1 的甲基化在结直肠癌（CRC）中较为常见。在诊断时，它们通常作为循环肿瘤 DNA（ctDNA）在血液中被检测到，并且在大多数 CRC 患者手术后会消失。进行了一项前瞻性研究，以确定手术后这些标志物的检测与残留疾病和复发的风险之间的关系。
在 CRC 手术切除后 12 个月内确定甲基化 BCAT1 和 IKZF1 的 ctDNA 状态，并将其与残留疾病的存在或风险（受累边缘、转移或淋巴结受累性质）以及无复发生存相关联。
手术后从 172 例 CRC 患者中采集了血液，其中 28 例（16%）ctDNA 阳性。在术后有临床随访的 138 例中，有 23 例诊断为复发（中位随访时间 23.3 个月，IQR 14.3-29.5）。多变量建模表明，提示残留疾病的特征是术后 ctDNA 状态的独立预测因素：具有三种特征之一（切除边缘接近、顶端淋巴结受累或远处转移）的病例发生 ctDNA 阳性的可能性是 5.3 倍（95%CI 1.5-18.4，p=0.008）。多变量分析表明，术后 ctDNA 阳性与复发风险增加独立相关（HR 3.8，1.5-9.5，p=0.004）。
手术后 ctDNA 阳性的 CRC 病例存在残留疾病和随后复发的风险增加。这可能对指导辅助治疗和监测策略的建议产生影响。现在需要进行随机研究，以确定监测这些生物标志物的病例是否会带来生存获益。
