Abstract Background Ankyrin repeat domain 53 (ANKRD53) plays an important role in maintaining chromosome integrity and stability, and chromosome instability is associated with cancer. Through integrative analysis, this study investigates the potential value of ANKRD53 in stomach adenocarcinoma (STAD). Methods RNA-seq and scRNA-seq data were used for integrative analysis based on online databases. Expression of ANKRD53 was confirmed by RT-PCR after bioinformatic analysis. Kaplan–Meier and Cox regression analyses were performed to evaluate the prognostic value of ANKRD53 in STAD. Gene set enrichment analysis (GSEA) was performed to evaluate ANKRD53-related signaling pathways. In addition, the interaction of ANKRD53 with immunity was also investigated. Results RT-PCR in STAD cell lines confirmed that ANKRD53 was downregulated in STAD samples compared to normal samples in the online databases. As an independent predictive biomarker, ANKRD53 was combined with other clinicopathological parameters to create a prognostic nomogram. Using GSEA, ANKRD53 was found to be involved in five pathways, including the TGF-β signaling pathway. Further investigation revealed that ANKRD53 was associated with immune checkpoint molecules, immunological pathways, and immunotherapy, in addition to MSI, TMB and neoantigens. In addition, scRNA-seq data revealed that ANKRD53 is mainly expressed in CD8+ T and dendritic cells. Conclusions ANKRD53 is an important biomarker for STAD that deserves further attention.
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