Faaborg Louise, Andersen Rikke Fredslund, Waldstrøm Marianne, Henriksen Jon Røikjær, Adimi Parvin, Jakobsen Anders, Steffensen Karina Dahl
Department of Oncology, Lillebaelt Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Department of Regional Health Research, University of Southern Denmark, J.B. Winsløws Vej 19, 5000 Odense C, Denmark.
Cancers (Basel). 2022 Mar 30;14(7):1766. doi: 10.3390/cancers14071766.
Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making.
甲基化同源盒A9循环肿瘤DNA（meth-HOXA9）已被提议作为上皮性卵巢癌（EOC）基于血液的生物标志物，尽管其预后意义尚未得到证实。本研究的目的是调查meth-HOXA9对复发性EOC患者的预后影响。从4 mL血浆中纯化DNA，经过亚硫酸氢盐转化后，使用甲基化特异性液滴数字PCR分析meth-HOXA9。meth-HOXA9的检测结果以总DNA的百分比和二元变量（可检测和不可检测）报告。以总生存（OS）作为主要终点，将meth-HOXA9状态及其在姑息治疗期间的动态变化与OS相关联。在基线时，65.9%（83/126）的患者检测到meth-HOXA9。基线时可检测和不可检测meth-HOXA9的患者的中位OS分别为8.9个月和17.9个月（风险比：2.04，p = 0.002），在多变量分析中仍具有显著性。一个治疗周期后meth-HOXA9升高的患者的中位OS为5.3个月，而meth-HOXA9不可检测的患者为33个月（p < 0.001）。meth-HOXA9与不良生存显著相关，可作为复发性EOC患者的预后标志物。从辅助临床决策的角度来看，对meth-HOXA9进行纵向监测在临床上是可行的。
