Unraveling the oncogenic and immunomodulatory roles of GINS1: a systematic pan-cancer study.

[BACKGROUND] GINS1 mediates DNA replication fidelity and cell cycle regulation through its integral role in the GINS complex. However, its comprehensive role across diverse cancer types remains unclear. This study aimed to systematically analyze the critical functions of GINS1 across cancers.

[METHODS] We utilized pan-cancer and multi-omics datasets and applied survival analysis, immune infiltration assessment, functional enrichment analysis, and genomic alteration profiling to explore.

[METHODS] We utilized pan-cancer and multi-omics datasets and applied survival analysis, immune infiltration assessment, functional enrichment analysis, and genomic alteration profiling to explore expression patterns, prognostic significance, immune infiltration, genomic alterations, and potential therapeutic relevance of GINS1 across multiple cancers. Ultimately, we evaluated the diagnostic performance of GINS1 in four cancer types and validated its functional role in renal cancer through in vitro assays, including colony formation, CCK-8, EdU, and Transwell, confirming that GINS1 knockdown inhibits cell proliferation and impairs PI3K/AKT pathway activity.

[RESULTS] GINS1 was significantly upregulated in 31 cancer types and correlated with poor prognosis in multiple malignancies. GINS1, as a biomarker, is concurrently linked to tumor mutational burden (TMB), microsatellite instability (MSI), and RNA m6A modification across tumor lineages. High GINS1 expression was significantly associated with distinct immune infiltration patterns, characterized by reduced NKT cell signatures and increased Th2 cell enrichment. Functional analysis revealed that GINS1 is involved in cell cycle regulation, DNA replication, and oncogenic signaling pathways (PI3K-Akt, p53, and NF-κB). Notably, survival analysis indicated that GINS1 expression affects the immunotherapy response, predicting poor outcomes in patients receiving anti-PD-1 therapy but an improved response to anti-PD-L1 inhibitors. GINS1 exhibited strong diagnostic value in KIRP, LIHC, PAAD, and SARC. In renal cancer, functional assays confirmed that GINS1 knockdown significantly suppressed cell proliferation, migration, and invasion, and attenuated PI3K/AKT signaling activity.

[CONCLUSION] GINS1 serves as a viable prognostic indicator and target for therapeutic intervention, influencing both tumor progression and immune regulation. Targeting GINS1 may provide new therapeutic insights for cancer management.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12935-026-04252-z.