Fig. 8
EV-packaged circBIRC6 association with DNA repair and chemoresistance in pancreatic cancer patients. (A) Depiction of representative ISH results for circBIRC6 and IHC for γH2AX in oxaliplatin-resistant (OXA-R, n = 51) and oxaliplatin-sensitive (OXA-S, n = 31) pancreatic cancer samples. Scale bars, 100 μm. (B-C) Quantitative breakdown of the specimen percentages featuring low or high expression of circBIRC6 (B) and γH2AX (C) across oxaliplatin-resistant and oxaliplatin-sensitive groups. (D) Quantification of the specimen percentages with low or high γH2AX expression within groups categorized by low or high circBIRC6 expression. (E) SUMOylated XRCC4, immunoprecipitated using the SUMO1 antibody, was analyzed by Western blot in OXA-R and OXA-S pancreatic cancer specimens. (F) Percentage distribution of samples with different SUMOylated XRCC4 levels grouped by circBIRC6 expression. (G) Distribution of samples based on SUMOylated XRCC4 expression within groups defined by oxaliplatin response. (H) Evaluation of plasma EV-packaged circBIRC6 expression using qRT–PCR in oxaliplatin-sensitive (OXA-S, n = 31) and oxaliplatin-resistant (OXA-R, n = 51) PDAC tissues. (I) Kaplan–Meier survival curves representing patients treated with platinum-based chemotherapy, categorized by high or low plasma EV-packaged circBIRC6 expression. (J) Kaplan–Meier survival curves representing patients undergoing chemotherapy without platinum, segregated by high or low plasma EV-packaged circBIRC6 expression. (K) Schematic illustration delineating the mechanism by which EV-packaged circBIRC6 contributes to CAFs’ promotion of oxaliplatin chemoresistance in pancreatic cancer. Data are presented as mean ± SD. ***p < 0.001