An Ning, Cui Li, Yang Xue
Department of Radiation Oncology, The Affiliated Hospital of Qingdao University Qingdao 266003, Shandong, China.
Department of Oncology, The People's Hospital of Pingyi County Linyi 273399, Shandong, China.
Am J Transl Res. 2023 Aug 15;15(8):5457-5468. eCollection 2023.
The current use of adjuvant radiotherapy in thymoma (THYM) following radical surgery is primarily based on clinical factors and is a subject of ongoing debate.
We developed a new biomarker, promotor methylation burden of Deoxyribonucleic acid repair genes (RPMB), to identify patients who may benefit from adjuvant radiotherapy after complete resection in THYM. RPMB quantitatively measures the promoter methylation level of Deoxyribonucleic acid (DNA) repair genes.
The methylation profile of 124 patients and corresponding clinical data were retrieved from The Cancer Genome Atlas (TCGA) database. The methylation level of DNA repair genes (DRGs) was found to be significantly hypomethylated juxtaposed to other genes across the whole human genome (all < 0.001). THYM patients with higher RPMB tended to be female ( = 1.114×10) and have a more advanced Masaoka stage ( = 0.034). Kaplan-Meier analysis showed that high RPMB could significantly predict a poor disease-free survival (DFS) in THYM patients who received adjuvant radiotherapy after complete resection (HR = 5.750, 95% CI: 1.213-27.251, = 0.013). Furthermore, Cox regression analysis indicated that RPMB was the only prognostic factor significantly associated with DFS after adjuvant radiotherapy ( = 0.028).
Low RPMB may be a potential indicator to identify suitable patients who can benefit from adjuvant radiotherapy in THYM, sparing others from treatment toxicity.
目前胸腺瘤(THYM)根治性手术后辅助放疗的应用主要基于临床因素,仍是一个持续争论的话题。
我们开发了一种新的生物标志物,即脱氧核糖核酸修复基因启动子甲基化负担(RPMB),以识别在胸腺瘤完全切除后可能从辅助放疗中获益的患者。RPMB定量测量脱氧核糖核酸(DNA)修复基因的启动子甲基化水平。
从癌症基因组图谱(TCGA)数据库中检索了124例患者的甲基化谱和相应的临床数据。发现DNA修复基因(DRGs)的甲基化水平与整个人类基因组中的其他基因相比显著低甲基化(所有P<0.001)。RPMB较高的胸腺瘤患者往往为女性(P = 1.114×10)且Masaoka分期更晚(P = 0.034)。Kaplan-Meier分析表明,高RPMB可显著预测胸腺瘤患者在完全切除后接受辅助放疗时无病生存期(DFS)较差(HR = 5.750,95%CI:1.213 - 27.251,P = 0.013)。此外,Cox回归分析表明,RPMB是辅助放疗后与DFS显著相关的唯一预后因素(P = 0.028)。
低RPMB可能是识别胸腺瘤中适合接受辅助放疗的患者的潜在指标,使其他患者免受治疗毒性。