Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma

Ruijia Liu,1,2,* Xudong Yu,1,* Xu Cao,1,2 Xuyun Wang,3 Yijun Liang,2 Wenying Qi,1,2 Yong’an Ye,1,2 Xiaobin Zao1,2,4 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 2Institute of Liver Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaobin Zao, Assistant Researcher, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Haiyuncang Road, Dongcheng District, Beijing, 100700, People’s Republic of China, Tel +86-10-8401-3194, Email A3417@bucm.edu.cnPurpose: ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC).Patients and Methods: Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments.Results: ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2.Conclusion: In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.Keywords: hepatocellular carcinoma, ST6GAL2, prognosis, immune cell infiltration, biomarker