Zheng Yang, Sun Hongyan, Cong Lele, Liu Chenlu, Sun Qian, Wu Nan, Cong Xianling
Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, China.
Biobank, China-Japan Union Hospital of Jilin University, Changchun, China.
J Oncol. 2021 May 4;2021:6660571. doi: 10.1155/2021/6660571. eCollection 2021.
Melanoma is the most aggressive form of skin cancer. Circulating tumor DNA (ctDNA) is a diagnostic and prognostic marker of melanoma. However, whether ctDNA mutations can independently predict survival remains controversial. This meta-analysis assessed the prognostic value of the presence or change in ctDNA mutations in melanoma patients.
We identified studies from the PubMed, EMBASE, Web of Science, and Cochrane databases. We estimated the combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) using either fixed-effect or random-effect models based on heterogeneity.
Sixteen studies including 1,781 patients were included. Both baseline and posttreatment detectable ctDNA were associated with poor OS (baseline detectable vs. undetectable, pooled HR = 1.97, 95% CI = 1.64-2.36, < 0.00001; baseline undetectable vs. detectable, pooled HR = 0.19, 95% CI = 0.11-0.36, < 0.00001; posttreatment detectable vs. undetectable, pooled HR = 2.36, 95% CI = 1.30-4.28, =0.005). For PFS, baseline detectable ctDNA may be associated with adverse PFS (baseline detectable vs. undetectable, pooled HR = 1.41, 95% CI = 0.84-2.37, =0.19; baseline undetectable vs. detectable, pooled HR = 0.43, 95% CI = 0.19-0.95, =0.04) and baseline high ctDNA and increased ctDNA were significantly associated with adverse PFS (baseline high vs. low/undetectable, pooled HR = 3.29, 95% CI = 1.73-6.25, =0.0003; increase vs. decrease, pooled HR = 4.48, 95% CI = 2.45-8.17, < 0.00001). The baseline BRAF ctDNA mutation-positive group was significantly associated with adverse OS compared with the baseline ctDNA-negative group (pooled HR = 1.90, 95% CI = 1.58-2.29, < 0.00001). There were no significant differences in PFS between the baseline BRAF ctDNA mutation-detectable group and the undetectable group (pooled HR = 1.02, 95% CI = 0.72-1.44, =0.92).
The presence or elevation of ctDNA mutation or BRAF ctDNA mutation was significantly associated with worse prognosis in melanoma patients.
黑色素瘤是最具侵袭性的皮肤癌形式。循环肿瘤DNA（ctDNA）是黑色素瘤的一种诊断和预后标志物。然而，ctDNA突变是否能独立预测生存仍存在争议。这项荟萃分析评估了黑色素瘤患者中ctDNA突变的存在或变化的预后价值。
我们从PubMed、EMBASE、科学网和Cochrane数据库中识别研究。我们根据异质性使用固定效应或随机效应模型估计总生存（OS）和无进展生存（PFS）的合并风险比（HRs）。
纳入了16项研究，共1781例患者。基线和治疗后可检测到的ctDNA均与较差的OS相关（基线可检测与不可检测，合并HR = 1.97，95%CI = 1.64 - 2.36，P < 0.00001；基线不可检测与可检测，合并HR = 0.19，95%CI = 0.11 - 0.36，P < 0.00001；治疗后可检测与不可检测，合并HR = 2.36，95%CI = 1.30 - 4.28，P = 0.005）。对于PFS，基线可检测到的ctDNA可能与不良PFS相关（基线可检测与不可检测，合并HR = 1.41，95%CI = 0.84 - 2.37，P = 0.19；基线不可检测与可检测，合并HR = 0.43，95%CI = 0.19 - 0.95，P = 0.04），且基线ctDNA水平高和ctDNA增加与不良PFS显著相关（基线高与低/不可检测，合并HR = 3.29，95%CI = 1.73 - 6.25，P = 0.0003；增加与减少，合并HR = 4.48，95%CI = 2.45 - 8.17，P < 0.00001）。与基线ctDNA阴性组相比，基线BRAF ctDNA突变阳性组与不良OS显著相关（合并HR = 1.90，95%CI = 1.58 - 2.29，P < 0.00001）。基线BRAF ctDNA突变可检测组与不可检测组之间的PFS无显著差异（合并HR = 1.02，95%CI = 0.72 - 1.44，P = 0.92）。
ctDNA突变或BRAF ctDNA突变的存在或升高与黑色素瘤患者较差的预后显著相关。
