A new plasmonic microarray platform detected clinically important KRAS mutations in blood and urine from patients with early colorectal cancer. The test showed complete agreement with tissue biopsy results under optimized testing conditions, suggesting a potential advance for liquid biopsy diagnostics.
The experimental assay, described in npj Precision Oncology, was designed to overcome one of the major limitations of current liquid biopsy technologies: the difficulty of detecting tiny amounts of circulating tumor DNA (ctDNA) in patients with early-stage disease. Instead of relying on conventional PCR or next-generation sequencing (NGS), the platform selectively amplifies mutant KRAS, which produces a strong plasmon-enhanced fluorescence signal.
The test targets KRAS mutations in codons 12, 13, 61, and 146 – biomarkers routinely used to guide anti-EGFR therapy decisions in colorectal cancer. Unlike many existing assays that require separate probes for individual variants, the new approach uses a single primer-probe set to detect all mutations within each target codon, simplifying assay design while maintaining specificity.
Researchers evaluated paired tissue, plasma, and urine samples from 58 patients, including 39 with malignant colorectal tumors, most of whom had stage 0-II disease. The microarray showed complete concordance with tissue KRAS status in all malignant mutation-positive tissue samples. In plasma, agreement was high but not perfect because a small number of tissue-negative cases produced positive results. In urine, increasing the amount of input DNA restored complete agreement between urine and tissue findings in malignant cases. Benign tumors rarely produced detectable mutations in blood or urine despite harboring KRAS alterations in tissue, consistent with lower ctDNA release rather than analytical failure.
The study also compared the platform with commercial assays. A tissue-approved PCR kit failed to detect plasma mutations in the evaluated malignant cases, while a research-use PCR assay identified more mutations but generated a substantial number of apparent false positives. Conventional liquid biopsy NGS likewise failed to detect plasma KRAS mutations in the predominantly early-stage cohort.
Although the findings require validation in larger, independent studies before clinical adoption, the work points toward a new generation of liquid biopsy assays capable of detecting molecular biomarkers earlier in disease. For clinical laboratories, improved analytical sensitivity without sacrificing specificity could expand the role of non-invasive testing for companion diagnostics, minimal residual disease monitoring, and longitudinal surveillance in colorectal cancer.
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