Early detection of renal cell carcinoma: a novel cell-free DNA fragmentomics‑based liquid biopsy assay

Cancer research · Renal cell carcinoma

The cfDNA fragmentomics‑based liquid biopsy achieves high sensitivity and specificity for early detection of renal cell carcinoma (RCC), providing a non‑invasive, cost‑effective diagnostic tool that distinguishes malignant renal tumors from benign conditions.

Renal cell carcinoma (RCC) is a growing global health challenge with poor survival rates in advanced stages due to the lack of effective early detection methods. This study developed a cell‑free DNA (cfDNA) fragmentomics‑based liquid biopsy to enable noninvasive RCC diagnosis. Using low‑pass whole‑genome sequencing, three cfDNA features—copy number variation, fragment size distribution, and nucleosome footprint—were integrated into a stacked ensemble machine‑learning model. The model achieved an area under the curve of 0.966 and 0.952 in the validation and external cohorts, with sensitivities of 90.5 % and 76.7 % and specificities of 93.8 % and 92.9 %. Robust performance was observed across different TNM stages, histological subtypes, and Fuhrman grades, with high sensitivity even for early‑stage RCC. The assay effectively differentiated malignant tumors from benign renal conditions, potentially reducing unnecessary surgeries. The cfDNA fragmentomics-based liquid biopsy is a promising, noninvasive, cost‑effective, and accurate approach for RCC detection and management, complementing conventional diagnostic techniques.

The cfDNA fragmentomics‐based liquid biopsy offers a noninvasive, cost‑effective, and accurate diagnostic approach for RCC, enabling early detection, reducing unnecessary surgical interventions, and improving clinical outcomes in a disease with poor survival when detected late.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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