By dividing CC samples into clusters and further investigating NAD+ metabolic-related genes implicated in CC progression, we pinpointed 21 prognostic NAD+ metabolic-related genes (ADAMTS10, ANGPTL5, APCDD1L, CCDC85A, CGREF1, CHRDL2, CRP, DENND5B, EFS, FGF8, P4HA3, PCDH20, PCDHAC2, RASGRF2, S100P, SLC19A3, SLC6A14, TESC, TFPI, TNMD, ZNF229) using univariate and multivariate regression analyses. Here, EFS is linked to cholangiocarcinoma.