Biomarker-directed aptamer panels for diagnosis and differentiation of neuroendocrine tumors

Neuroendocrine tumors (NETs) are rare tumors that may arise in the small intestine (siNET) or pancreas (pNET). The tumors have heterogeneous clinical characteristics, and diagnosis may be challenging. Current non-invasive biomarkers perform suboptimally, and novel biomarkers are highly needed. We aimed to investigate the use of RNA aptamer panels, selected by the APTASHAPE technology, in distinguishing healthy individuals from individuals with NET as well as discriminating siNET from pNET. Plasma samples from 68 individuals with NET and 24 healthy individuals were collected and randomly divided into a development set and a test set. A panel of aptamers recognizing disease-specific plasma proteins was selected in the development set, and the accuracy for disease prediction was evaluated in the test set. The aptamer panels demonstrated high discriminative power, accurately distinguishing between healthy individuals and NET patients with AUCs of 0.74 and 0.87 in the development set and test set, respectively. Furthermore, the aptamer panels were able to differentiate between siNET and pNET patients with AUCs of 0.72 in both the development set and the test set. In addition, mass spectrometry analysis identified ITIH2 and IGHG3 as potential novel biomarkers for the diagnosis of NET. The APTASHAPE platform is a capable tool for selecting protein biomarker-directed aptamer panels for the diagnosis of NET and discrimination between siNET and pNET. Furthermore, the identification of ITIH2 and IGHG3 highlights the potential of APTASHAPE to identify novel protein biomarkers in NET.