Background: Liquid biopsy using plasma cfDNA has been established as a tool for informing the management of advanced-stage NSCLC. However, its effectiveness in early lung cancer detection, including the identification of high-risk cases, remains to be determined. Methods: We analyzed plasma cfDNA and matched tumors from 117 stage I–IV lung adenocarcinoma cases and compared the variants identified across all stages using the Oncomine Precision Assay on the GenexusTMnext-generation sequencing platform. Results: Cancer-specific mutations were detected in plasma from approximately 72% (84/117) of cases (all stages), with detection rates increasing by stage. Concordance between cfDNA and tumor tissue also increased with stage 0% (stage I), 19% (stage II), 45% (stage III), and 75% (stage IV).KRASmutations were concordant in approximately 22% (6/27) of stage II and 46% (11/24) of stage III cases. Clinically importantEGFRvariants showed concordance in 11% (1/9) of stage II and 80% (8/10) in stage III/IV cases. Actionable mutations, targetable with FDA-approved drugs, were detected in 11% (4/37) of stage II, 27% (12/45) of stage III, and 55% (4/9) of stage IV cases, underscoring the potential of liquid biopsy for early detection of therapeutic targets. Moreover, co-occurring mutations with varying actionability were identified more frequently in plasma than in tumor tissues. Plasma detection of clinically importantKRASandEGFRvariants was mostly associated with advanced-stage disease, suggesting the presence of these variants in plasma as a potential indication of disease progression. Conclusions: Liquid biopsy holds promise for identifying high-risk lung adenocarcinoma cases and serves as a complementary diagnostic tool in advanced stages, enhancing disease management strategies.
背景：利用血浆循环游离DNA（cfDNA）进行液体活检，已成为指导晚期非小细胞肺癌（NSCLC）管理的一种工具。然而，其在早期肺癌检测（包括高风险病例识别）中的有效性仍有待确定。方法：我们分析了117例I–IV期肺腺癌患者的血浆cfDNA及匹配肿瘤组织样本，并使用GenexusTM新一代测序平台上的Oncomine Precision Assay，比较了各阶段检测到的变异情况。结果：在所有分期病例中，约72%（84/117）的血浆样本中检测到癌症特异性突变，且检出率随分期升高而增加。cfDNA与肿瘤组织检测结果的一致性也随分期上升而提高：I期为0%，II期为19%，III期为45%，IV期为75%。在II期病例中，约22%（6/27）的KRAS突变检测结果一致；在III期病例中，这一比例为46%（11/24）。具有临床重要意义的EGFR变异在II期病例中的一致性为11%（1/9），在III/IV期病例中为80%（8/10）。在II期病例中，11%（4/37）检测到可用FDA批准药物靶向的治疗相关突变；III期病例中为27%（12/45）；IV期病例中为55%（4/9），这凸显了液体活检在早期发现治疗靶点方面的潜力。此外，与肿瘤组织相比，血浆中更频繁地检测到具有不同可干预性的共现突变。临床上重要的KRAS和EGFR变异在血浆中的检测主要与晚期疾病相关，表明血浆中存在这些变异可能提示疾病进展。结论：液体活检有望用于识别高风险肺腺癌病例，并可作为晚期阶段的补充诊断工具，从而优化疾病管理策略。
Identification of Driver Mutations and Risk Stratification in Lung Adenocarcinoma via Liquid Biopsy
肿瘤(癌症)患者之家