Clinical performance of liquid RNA (L-RNA) biopsy in a gastrointestinal cancer segment.

Abstract

27 Background: Exosomal RNAs mediate cellular communication, reflect dynamic physiological and pathological changes. Unlike tissue biopsies, which may introduce confounding variables, exosomal RNA provides real-time insights into tumor activity. Standard GI cancer surveillance—using CEA, CA19-9, imaging, and endoscopy—has limitations: CEA may remain normal during relapse, CA19-9 can be elevated in benign conditions, and CT imaging sensitivity for peritoneal metastases is low (28.3%). CTOAM’s Liquid RNA (L-RNA) assay capitalizes on tumor-derived exosomal RNA. Unlike relatively static DNA, RNA expression dynamically reflects cellular and functional changes, providing real-time biological insights. Methods: A retrospective analysis was conducted on 21 patients using CTOAM’s L-RNA assay, which qualifies and quantifies exosomal RNA in blood via Genestudio S5 Prime with Ampliseq RNA NGS. Its proprietary method quantifies exosomal RNA expression in blood, enabling clear separation of interpatient variability in normal tissue from tumor-related variability. Results: Of 21 patients, 12 had results correlating with GI carcinoma (Colorectal-6, Pancreatic-4, Cholangiocarcinoma-2), 1 was inconclusive, and 8 were true negatives. The L-RNA assay demonstrated: Sensitivity: 100% (95% CI: 75.8–100); Accuracy: 87% (95% CI: 67.9–95.5); Precision (PPV): 80% (95% CI: 54.8–93); AUC: 86.4 (95% CI: 56.8–95.1). Tumor cell activity correlated with CPS values ranging from 367 (low) to 5,290 (high). Importantly, disease progression was detected 1–10 weeks earlier than with standard imaging (median lead time gain: 5 weeks). Conclusions: CTOAM’s L-RNA biopsy serves as a complement to biopsy or imaging and tissue/blood analyses. By monitoring disease progression and providing earlier prognostic insights, it may significantly improve clinical decision-making in GI cancers. CTOAM’s blood-based exosomal L-RNA analysis provides a non-invasive, earlier signal for tumor cell activity and relapse risk, often weeks ahead of conventional imaging. Further validation in larger cohorts is warranted. L-RNA data. Metric L-RNA vs Biopsy+Imaging+Blood (%) 95% CI L-RNA vs Blood biomarkers (%) 95% CI Sensitivity 100 (75.8-100) 100 (70.1-100) Specificity 72.7 (43.4-90.3) 72.7 (43.4-90.3) PPV (Precision) 80 (54.8-93) 75 (46.8-91.1) NPV 100 (67.6-100) 100 (67.6-100) Accuracy 87 (67.9-95.5) 85 (64-94.8) F1 Score 88.9 (63.6-96.3) 85.7 (56.1-95.3) AUC 86.4 (56.8-95.1) 86.4 (56.8-95.1)