Background: Mutations in theKRASgene play a pivotal role in lung cancer development and progression and are becoming increasingly important in therapeutic decision-making. The detection of these mutations in circulating tumor DNA (ctDNA) has attracted attention as a minimally invasive diagnostic approach. However, the accuracy reported in different studies varies widely.Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA-DTA guidelines. Eligible studies evaluated the detection ofKRASmutations in ctDNA in plasma or serum for lung cancer diagnosis and reported sufficient data to construct 2 × 2 contingency tables. Primary pooled estimates of sensitivity, specificity and likelihood ratios were calculated using aggregated 2 × 2 contingency tables. Additionally, a bivariate random-effects model was applied in a secondary analysis to investigate between-study heterogeneity.Results: Nine diagnostic study arms comprising 691 patients met the inclusion criteria. Across all datasets, there were 255 true positives, 19 false positives, 136 false negatives, and 281 true negatives. The pooled sensitivity was 65.2%, while the pooled specificity was 93.7%. The positive likelihood ratio was 10.35, and the negative likelihood ratio was 0.37, resulting in a diagnostic odds ratio of 28.0, which indicates strong rule-in capability. Sensitivity showed moderate heterogeneity across studies. In contrast, specificity demonstrated minimal heterogeneity.Conclusions: ctDNA-based detection ofKRASmutations demonstrates high specificity but moderate sensitivity for diagnosing lung cancer. These findings suggest that aKRASliquid biopsy could be a valuable complementary diagnostic tool, particularly when a tissue biopsy is not possible or is inadequate, and it could support more personalized decision-making as analytical technologies continue to advance.
背景：KRAS基因突变在肺癌发生发展中起着关键作用，且对治疗决策日益重要。通过循环肿瘤DNA（ctDNA）检测这些突变作为一种微创诊断方法已受到关注。然而，不同研究报告的准确性差异较大。
方法：我们根据PRISMA-DTA（诊断试验准确性系统评价指南）进行了系统评价和荟萃分析。纳入研究评估了血浆或血清中ctDNA的KRAS突变检测用于肺癌诊断，并报告了足够数据以构建2×2列联表。使用汇总的2×2列联表计算敏感性、特异性和似然比的主要合并估计值。此外，在二次分析中应用双变量随机效应模型以探究研究间的异质性。
结果：共9项诊断研究（涉及691名患者）符合纳入标准。所有数据集中，真阳性255例、假阳性19例、假阴性136例、真阴性281例。合并敏感性为65.2%，合并特异性为93.7%。阳性似然比为10.35，阴性似然比为0.37，诊断比值比为28.0，显示出较强的确诊能力。敏感性在不同研究间存在中度异质性，而特异性异质性极小。
结论：基于ctDNA的KRAS突变检测在诊断肺癌时表现出高特异性但中等敏感性。这些发现表明，KRAS液体活检可成为一种有价值的补充诊断工具，尤其在无法进行组织活检或组织样本不足时，且随着分析技术的持续进步，它将有助于实现更个性化的临床决策。
KRASMutations in Circulating Tumor DNA for Lung Cancer Diagnosis: A Comprehensive Meta-Analysis
肿瘤(癌症)患者之家