Blood transcriptional signatures of gallstone pathogenesis in patients with cholelithiasis and choledocholithiasis Running Title: Blood gene expression gallstone

Objective Disease-specific molecular signalling in peripheral blood has the potential to inform on pathophysiological mechanisms of diseases. Here, we aimed investigate blood-based gene expression profiles that reflect disease-specific pathogenic gallstones, such as antioxidant defence, heat-shock responses, DNA damage and repair, ABC pump mechanisms, mucin signals, mitochondrial dysfunction apoptosis patients with Cholelithiasis (CHL) Choledocholithiasis (CHDL) Materials Methods The relative fold-change mRNA levels 73 genes were analysed using a gallstone-related qRT-PCR array 10 control individuals, 24 CHL 23 CHDL patients. Serum malondialdehyde was determined by thiobarbituric-acid reactive substance assays, 8-hydroxy-2’-deoxyguanosine ELISA assays. Results Our results showed whole profile strongly reflects tissue specific gallstone pathogenesis. present findings altered expressions including defence (CuZn-SOD, CAT), heat shock protein (HSP70), repair (MLH1 RAD18), pro-apoptotic (P53, BAX, Cyt-c Caspase 3), transporter (ABCB1, ABCC2, LRP1) Mucin signals (MUCIN4, MUCIN5AC MUCIN5B) point out damages via oxidative stress well deteriorating types may also suggest activation mitophagy activator, DRP1/hFIS1/PINK1 axis induced have role pathogenesis CHDL. Conclusions indicate signature promising accuracy for monitorize disease patients, unaffected controls.