Global mRNA 3'UTR lengthening in small-cell neuroendocrine carcinoma

Small-cell neuroendocrine carcinoma (SCNC) is a rare but highly malignant tumor subtype, primarily arising in the lung and prostate. The convergence of SCNCs across diverse tissues enables their identification through conserved SCNC-specific molecular markers, facilitating tumor subtype classification. As a critical post-transcriptional regulatory mechanism, alternative polyadenylation (APA) is involved in various biological processes, especially in tumor progression. However, its role across tumor subtypes remains unclear. Here, we revealed a global 3'UTR lengthening pattern due to APA in the SCNCs. We identified a set of conserved lengthening 3'UTR events across SCNCs originating from different tissues, showing a high association with neural development and related signaling pathways. More broadly, we developed a prediction model using a neural network framework to identify SCNCs based on the SCNC-specific APA signatures as additional molecular markers. Our work provides new insights into the post-transcriptional landscape of SCNCs and establishes APA as a potential biomarker for SCNC identification.