ArticleCancer medicine2025
Tumor Genomic and Transcriptomic Analysis Integrated With Liquid Biopsy ctDNA Monitoring: Analytical Validation and Clinical Insights.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
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- Tumor Genomic and Transcriptomic Analysis Integrated With Liquid Biopsy ctDNA Monitoring: Analytical Validation and Clinical Insights.Cancer medicine · 2025Article
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17 authors.
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Abstract
backgroundComprehensive genomic profiling (CGP) is a time- and tissue- efficient method to help guide precision oncology. To enhance the clinical utility of CGP, we investigated the performance of a novel strategy integrating tumor DNA and mRNA profiling, together with liquid biopsy ctDNA monitoring.
methodsGenomic DNA and mRNA simultaneously extracted from 604 archived tissue samples of 12 cancer types were used. Tumor DNA was subjected to targeted sequencing using a 504-gene panel with high-density probes (HDP), and shallow whole genome sequencing to profile genomic biomarkers. mRNA transcriptome profiling was performed to further capture fusion variants, and to predict tissue of origin (TOO) using our ensemble model OriCUP, an algorithm trained on 9889 samples and independently validated on 731 samples. In a cohort of 55 metastatic lung cancer patients, longitudinal plasma ctDNA was analyzed using a hybrid tumor-informed and tumor-agnostic approach to predict progression-free survival (PFS).
resultsAmong all biomarkers, DNA sequencing using HDP achieved higher sensitivity than the standard panel design to identify copy number variations at chromosome-, gene-, and exon- levels. The detection rate of fusion variants using DNA sequencing alone was 20% lower than mRNA sequencing in reference samples, while the combination of both methods was essential to maximize fusion detection in clinical FFPE samples. For TOO, our OriCup model achieved prediction accuracy of 87.7% for primary tumors and 81.4% for metastatic tumors. In 55 lung cancer patients, ctDNA profiling identified additional 11.5% tumor-agnostic actionable and resistance mutations. Patients having more than 50% ctDNA decrease from baseline were classified as molecular responders and showed significantly longer PFS than those classified as molecular non-responders (HR = 9.42, 95% CI: 3.33-26.67, p < 0.0001, 12-month PFS: 95.5% vs. 31.7%).
conclusionsComprehensive genomic and transcriptomic profiling could reliably unveil genetic details not provided by DNA-only CGP. The integration of ctDNA detection further helped detect tumor-agnostic mutations and monitor treatment response.
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