Abstract
BACKGROUND: Gallbladder neuroendocrine carcinoma (NEC) represents a subtype of gallbladder malignancies characterized by a low incidence, aggressive nature, and poor prognosis. Despite its clinical severity, the genetic alterations, mechanisms, and signaling pathways underlying gallbladder NEC remain unclear. CASE SUMMARY: This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient, who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V. Targeted gene sequencing and bioinformatics analysis tools, including STRING, GeneMANIA, Metascape, TRRUST, Sangerbox, cBioPortal and GSCA, were used to analyze the biological functions and features of mutated genes in gallbladder NEC. Twelve mutations (APC, ARID2, IFNA6, KEAP1, RB1, SMAD4, TP53, BTK, GATA1, GNAS, and PRDM3) were identified, and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing. A protein-protein interaction network showed significant interactions among the twelve mutated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways. The results revealed 40 tumor-related pathways. A key regulatory factor for gallbladder NEC-related genes was identified, and its biological functions and features were compared with those of gallbladder carcinoma. CONCLUSION: Gallbladder NEC requires standardized treatment. Comparisons with other gallbladder carcinomas revealed clinical phenotypes, molecular alterations, functional characteristics, and enriched pathways.