作者与单位 Authors & Affiliations
Zefeng Xie1, Yuze Zhao1, Haitao Li1, Yu Li1, Yulan Chen2, Meilian Liu3, Xuyuan Li4
1Department of Thoracic Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou City, China,2Department of Oncology, The First People's Hospital of Zhaoqing, Zhaoqing City, China,3Department of Pulmonary Oncology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang City, China,4Department of Oncology, Shantou Central Hospital, Shantou City, China
摘要 Abstract
Background: Although amplicon-based DNA+RNA NGS co-detection has demonstrated clear advantages over hybrid-capture DNA-NGS for identifying gene fusions in non-small cell lung cancer (NSCLC), the clinical relevance of single-nucleotide variants (SNVs) and small insertions/deletions (INDELs) in NSCLC remains equally critical for precision oncology. However, whether amplicon-based DNA+RNA NGS co-detection provides comparable or improved performance for detecting NSCLC driver-gene SNVs/INDELs relative to hybrid-capture DNA-NGS has not been systematically evaluated.
Methods: We performed a comparative analysis of SNV and INDEL detection across 19 clinically relevant NSCLC driver genes, including AKT1, ALK, ARAF, BRAF, EGFR, ERBB2, FGFR1/2, HRAS, IDH1/2, KIT, KRAS, MAP2K1, MET, MTOR, NRAS, NTRK, PDGFRA, PIK3CA, and RET. Detection rates generated by a 35-gene amplicon-based DNA+RNA NGS co-detection assay (n = 2,242) were compared with those obtained using hybrid-capture DNA-NGS (n = 2,504).
Results: Amplicon-based DNA+RNA NGS co-detection demonstrated significantly higher detection rates for EGFR (50.68% vs 45.73%, P < 0.05), KRAS (12.25% vs 10.78%, P < 0.05), and KIT (0.40% vs 0.08%, P < 0.05) compared with hybrid-capture DNA-NGS. The increase in EGFR detection was primarily driven by improved identification of EGFR L858R (23.39% vs 20.01%, P < 0.05). For KRAS, differences were mainly contributed by KRAS G12C (4.12% vs 3.75%) and G12D (2.43% vs 1.80%), though these did not reach statistical significance. In contrast, hybrid-capture DNA-NGS showed a significantly higher detection rate for PIK3CA (6.11% vs 4.51%, P < 0.05). For all remaining genes, including AKT1(0.32% vs 0.28%), ALK(0.11% vs 0.12%), ARAF(0.12% vs 0.12%), BRAF(2.89% vs 2.6%), ERBB2(2.98% vs 3%), FGFR2(0.08% vs 0.08%), FGFR3(0.21% vs 0.16%), HRAS(0.08% vs 0.16%), IDH1(0.28% vs 0.28%), IDH2(0.12% vs 0.12%), MAP2K1(0.31% vs 0.48%), MET(0.52% vs 0.52%), MTOR(0.26% vs 0.32%), NRAS(0.41% vs 0.52%), NTRK(0.01% vs 0.04%), PDGFRA(0.12% vs 0.16%), RET(0.1% vs 0.12%), the mutation detection rates showed no significant difference between the two platforms.
Conclusion: This large-cohort comparison demonstrates that amplicon-based DNA+RNA NGS co-detection performs comparably to hybrid-capture DNA-NGS for most NSCLC driver-gene SNV/INDEL alterations, while offering significantly higher sensitivity for critical mutations in EGFR, KRAS, and KIT. These findings indicate that co-detection workflows integrating both DNA and RNA may improve mutation detection efficiency for key actionable NSCLC biomarkers, supporting their broader adoption in routine clinical genomic profiling.