SLC35G2 as a Prognostic Biomarker in Hepatocellular carcinoma and Its Correlation with Immunity

Abstract

Abstract Hepatocellular carcinoma (HCC) is the major cause of the worldwide cancer burden, especially in China. Solute Carrier Family 35 Member G2 (SLC35G2), a methylation-related gene, plays an essential role during tumorigenesis. However, its roles in key biological functions, the tumor microenvironment, mutations, and single-cell sequencing analysis remain unclear in HCC. This study aimed to identify the correlation between SLC35G2 and prognosis, biological roles, and immune features in HCC. The abnormal expression of SLC35G2 was associated with multiple tumor types, and there was a significant upregulation in HCC samples compared to normal tissues, which was an independent prognostic factor for predicting poor overall survival (OS) and disease-specific survival (DSS) in HCC. A nomogram based on SLC35G2, age, gender, histologic grade, and T-, N-, and M-stages was constructed, and the prognostic model performed well as shown by calibration curves for the 1-, 3-, and 5-year OS. Gene set enrichment analysis showed that SLC35G2 was closely related to tumorigenesis and immune response pathways, including Hippo-merlin, PI3K-AKT, IL-8, and IL-10 signaling pathways. In addition, SLC35G2 expression was inversely correlated with eosinophils and Th17 cells, and increased SLC35G2 expression was significantly associated with immune checkpoint molecules (GI24, CTLA4, PD-L1, B7-H3, TIM-3, and TGF-β). Furthermore, single-cell sequencing analysis showed that SLC35G2 expression was primarily localized in NK/T cells. In conclusion, SLC35G2 was identified as a new prognostic marker and had important potential implications for immunotherapy in HCC.