Integrated GMPS and RAMP3 as a signature to predict prognosis and immune heterogeneity in hepatocellular carcinoma.

• The GMPS|RAMP3 can predict the prognosis and assess the immune heterogeneity of patients with HCC. • The GMPS|RAMP3 is closely related to cell cycle and tumor angiogenesis. • The GMPS|RAMP3 effectively overcomes the technical bias and biological heterogeneity arising from different platforms by utilizing relative gene expression levels. Hepatocellular carcinoma (HCC) is a highly fatal malignant worldwide. As different expression levels of specific genes can lead to different HCC outcomes, we aimed to develop a gene signature capable of predicting HCC prognosis. In this study, transcriptomic sequencing and relevant clinical data were extracted from public platforms. The guanine monophosphate synthase (GMPS)|receptor activity-modifying protein 3 (RAMP3) gene pair was developed based on the relative values of gene expression levels. Nomograms were developed using R software. Immune status was assessed through single‐sample gene set enrichment analysis. GMPS knockdown was achieved through siRNA transfection. Quantitative reverse transcription PCR, apoptosis assays, and cell proliferation were performed to verify the function of GMPS|RAMP3 in HCC cells. Here, a gene pair containing GMPS and RAMP3 was successfully constructed. We demonstrated that the GMPS|RAMP3 gene pair was an independent predictor with strong prognostic prediction power, based on which a nomogram was established. Functional analysis revealed that the enrichment of cell cycle-related pathways and immune status differed considerably between the two groups, with cell cycle-related genes highly expressed in the high GMPS|RAMP3 value group. Finally, cell experiments indicated that GMPS knockdown significantly repressed proliferation, promoted apoptosis, and enhanced the sensitivity of HCC cells to gemcitabine. The gene pair GMPS|RAMP3 is a novel prognostic predictor of HCC, providing a promising approach to the treatment and assessment of immune heterogeneity in HCC. [ABSTRACT FROM AUTHOR]