SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that is over-expressed in HCC samples compared to normal liver tissue, and this observed overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of in TCGA-LIHC patients ( = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as , , and , while simultaneously inhibiting tumor suppressors including , , and . Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort ( = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with 'normal' paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.