Harnessing minimal residual disease for precision medicine in locally advanced gastric cancer

Table 1 Key characteristics of polymerase chain reaction-based and next-generation sequencing-based circulating tumor DNA analysis technologies

	ddPCR-based ctDNA-MRD assay	NGS-based ctDNA-MRD assay
Core technical principle	Microdroplet-partitioned single-molecule PCR amplification, absolute quantification of ctDNA mutations based on Poisson distribution[25,26]	Target region capture + high-throughput sequencing, combined with UMI for ctDNA mutation quantification[25,27]
LOD	0.01%-0.1% VAF[26]	0.1%-0.5% VAF (standard depth); < 0.01% VAF (ultra-deep sequencing)[27]
Detectable variant types	Only pre-designed known SNV and insertions/deletions (indel)[25,26]	Simultaneous detection of SNV, indel, CNV, and gene fusions[25,27]
Detection turnaround time	1-3 working days	5-7 working days
Single sample detection cost	Low (approximately 100-300 USD per sample)	Medium-high (approximately 500-1500 USD per sample)
Core advantages	Simple operation, low cost, short detection cycle, high absolute quantification accuracy[25,26]	Covers multi-gene and multi-variant types, tracks tumor heterogeneity, adapts to personalized panel design[25,27]
Core limitations	Only detects known mutations, cannot cover tumor heterogeneity, low throughput[25,26]	Long detection cycle, high cost, complex data analysis, lower sensitivity than ddPCR at standard sequencing depth[25,27]

ddPCR: Droplet digital polymerase chain reaction; ctDNA: Circulating tumor DNA; MRD: Minimal residual disease; NGS: Next-generation sequencing; PCR: Polymerase chain reaction; UMI: Unique molecular identifier; LOD: Limit of detection; VAF: Variant allele frequency; SNV: Single nucleotide variants; Indel: Insertion and deletion; CNV: Copy number variations.