Fig. 8: SRI may be the driver gene in the pathogenesis of PCAND.

During PC genesis and development, a variety of driver gene mutations (KRAS, CDKN2A, TP53 and SMAD4) and signaling pathway deregulation participate in the progression from pancreatic intraepithelial neoplastic lesions (PanINs 1-3) to PDAC. KRAS mutation is the initiating genetic event for PC, and the progression of normal pancreatic tissue to PDAC involves a stepwise genetic transition projected to span more than 10 years. PCAND is defined as PDAC with new-onset diabetes diagnosed within 2–3 years prior, so abnormal activation of the sorcin-STAT3 positive feedback loop may occur during the progression from PanIN 1-3 to PDAC, later than oncogene mutation. Downstream inflammatory cytokines/chemokines (such as CCL5 and serpin E1) may be potential biomarkers.