Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
Institute of Thoracic Oncology, Fudan University, Shanghai, China.
Cancer Med. 2021 Dec;10(23):8377-8386. doi: 10.1002/cam4.4339. Epub 2021 Oct 19.
GROWING EFFORTS ARE BEING INVESTED IN INVESTIGATING VARIOUS MOLECULAR APPROACHES TO DETECT MINIMAL RESIDUAL DISEASE (MRD) AND PREDICT DISEASE RECURRENCE. IN OUR STUDY, WE INVESTIGATED THE UTILITY OF PARALLEL LONGITUDINAL ANALYSIS OF MUTATION AND DNA METHYLATION PROFILES FOR PREDICTING MRD IN POSTOPERATIVE NON-SMALL-CELL LUNG CANCER (NSCLC) PATIENTS. TUMOR TISSUES AND LONGITUDINAL BLOOD SAMPLES WERE OBTAINED FROM 65 PATIENTS WITH RESECTED STAGE IA-IIIB NSCLC. SOMATIC MUTATION AND DNA METHYLATION PROFILING WERE PERFORMED USING ULTRA-DEEP TARGETED SEQUENCING AND TARGETED BISULFITE SEQUENCING, RESPECTIVELY. DYNAMIC CHANGES IN PLASMA-BASED MUTATION AND TUMOR-INFORMED METHYLATION PROFILES, REFLECTED AS MRD SCORE, WERE OBSERVED FROM BEFORE SURGERY (BASELINE) TO POSTOPERATIVE FOLLOW-UP, REFLECTING THE DECREASE IN TUMOR BURDEN OF THE PATIENTS WITH RESECTED NSCLC. MUTATIONS WERE DETECTED FROM PLASMA SAMPLES IN 63% OF THE PATIENTS AT BASELINE, WHICH SIGNIFICANTLY REDUCED TO 23-25% DURING POST-OPERATIVE FOLLOW-UPS. MRD SCORE POSITIVE RATE WAS 95.7% AT BASELINE, WHICH REDUCED TO 74% AT THE FIRST AND 70% AT THE SECOND FOLLOW-UP. AMONG THE 5 RELAPSED PATIENTS WITH PARALLEL LONGITUDINAL ANALYSIS OF MUTATION AND METHYLATION PROFILE, ELEVATED MRD SCORE WAS OBSERVED AT FOLLOW-UP BETWEEN 0.5-7 MONTHS PRIOR TO RADIOLOGIC RECURRENCE FOR ALL 5 PATIENTS. OF THEM, 4 PATIENTS ALSO HAD CONCOMITANT INCREASE IN ALLELIC FRACTION OF MUTATIONS IN AT LEAST 1 FOLLOW-UP TIME POINT, BUT ONE PATIENT HAD NO MUTATION DETECTED THROUGHOUT ALL FOLLOW-UPS. OUR RESULTS DEMONSTRATE THAT LONGITUDINAL PROFILING OF MUTATION AND DNA METHYLATION MAY HAVE POTENTIAL FOR DETECTING MRD AND PREDICTING RECURRENCE IN POSTOPERATIVE NSCLC PATIENTS.
正在投入更多努力，通过研究各种分子方法来检测微小残留病灶 (MRD) 并预测疾病复发。在我们的研究中，我们探讨了同时分析突变和 DNA 甲基化图谱在预测术后非小细胞肺癌 (NSCLC) 患者 MRD 中的效用。从 65 例接受 NSCLC 手术的 IA-IIIB 期患者中获得肿瘤组织和纵向血液样本。分别使用超深度靶向测序和靶向亚硫酸氢盐测序进行体细胞突变和 DNA 甲基化分析。从手术前 (基线) 到术后随访，观察到基于血浆的突变和肿瘤信息甲基化图谱的动态变化，反映为 MRD 评分，反映了切除 NSCLC 患者的肿瘤负荷降低。在基线时，从 63%的患者的血浆样本中检测到突变，在术后随访期间，该比例显著降低至 23-25%。基线时，MRD 评分阳性率为 95.7%，第一次随访时降至 74%，第二次随访时降至 70%。在进行突变和甲基化图谱平行纵向分析的 5 例复发患者中，所有患者均在影像学复发前 0.5-7 个月的随访中观察到升高的 MRD 评分。其中，4 例患者在至少 1 个随访时间点的突变等位基因分数也同时增加，但 1 例患者在所有随访中均未检测到突变。我们的结果表明，突变和 DNA 甲基化的纵向分析可能具有检测术后 NSCLC 患者 MRD 和预测复发的潜力。
