Wen Sara Witting Christensen, Wen Jan, Hansen Torben Frøstrup, Jakobsen Anders, Hilberg Ole
Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark.
Department of Regional Health Research, J.B. Winsloews Vej 19, 3rd Floor, 5000 Odense C, Denmark.
Cancers (Basel). 2022 Apr 30;14(9):2254. doi: 10.3390/cancers14092254.
This systematic review investigated circulating methylated tumor DNA in bronchial lavage fluid for diagnosing lung cancer. PROSPERO registration CRD42022309470. PubMed, Embase, Medline, and Web of Science were searched on 9 March 2022. Studies of adults with lung cancer or undergoing diagnostic workup for suspected lung cancer were included if they used bronchial lavage fluid, analyzed methylated circulating tumor DNA, and reported the diagnostic properties. Sensitivity, specificity, and lung cancer prevalence were summarized in forest plots. Risk of bias was assessed using the QUADAS-2 tool. A total of 25 studies were included. All were case-control studies, most studies used cell pellet for analysis by quantitative PCR. Diagnostic sensitivity ranged from 0% for a single gene to 97% for a four-gene panel. Specificity ranged from 8% for a single gene to 100%. The studies employing a gene panel decreased the specificity, and no gene panel had a perfect specificity of 100%. In conclusion, methylated circulating tumor DNA can be detected in bronchial lavage, and by employing a gene panel the sensitivity can be increased to clinically relevant levels. The available evidence regarding applicability in routine clinical practice is limited. Prospective, randomized clinical trials are needed to determine the further usefulness of this biomarker.
本系统评价研究了支气管灌洗液中循环甲基化肿瘤DNA用于诊断肺癌的情况。PROSPERO注册号为CRD42022309470。于2022年3月9日检索了PubMed、Embase、Medline和Web of Science。纳入了对患有肺癌或因疑似肺癌接受诊断检查的成年人的研究，条件是这些研究使用了支气管灌洗液、分析了甲基化循环肿瘤DNA并报告了诊断特性。敏感性、特异性和肺癌患病率在森林图中进行了总结。使用QUADAS-2工具评估偏倚风险。共纳入25项研究。所有研究均为病例对照研究，大多数研究使用细胞沉淀通过定量PCR进行分析。诊断敏感性范围从单个基因的0%到四基因组合的97%。特异性范围从单个基因的8%到100%。采用基因组合的研究降低了特异性，且没有基因组合具有100%的完美特异性。总之，支气管灌洗液中可检测到甲基化循环肿瘤DNA，通过采用基因组合，敏感性可提高到临床相关水平。关于其在常规临床实践中适用性的现有证据有限。需要进行前瞻性随机临床试验来确定该生物标志物的进一步实用性。
