Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non‐invasive diagnosis method based on serum markers, such as α‐fetoprotein (AFP), and des‐γ‐carboxy‐prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere‐coated three‐dimensional (3D) hierarchical porous chip, named a SiO2‐chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non‐HCC and HCC subjects are enriched using an SiO2‐chip and performed RNA sequencing to identify HCC‐related long non‐coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT‐1 and EGFR‐AS‐1 are two HCC‐related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT‐PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy‐based approach for noninvasive and reliable HCC detection is developed. Hepatocellular carcinoma (HCC), a deadly tumor, lacks effective non‐invasive diagnosis via current serum markers. The innovative SiO2‐chip enriches exosomes efficiently, unveiling HCC‐specific lncRNAs like LUCAT‐1 and EGFR‐AS‐1. Validated by qRT‐PCR, integrating these lncRNAs with traditional markers significantly enhances diagnostic accuracy. Moreover, their combination with DCP aids in monitoring HCC progression. This liquid biopsy approach offers reliable non‐invasive HCC detection.