SUMO-Activating Enzyme Subunit 1 (SAE1) is A Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

Abstract

Background: 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 SAE1 in glioma in a stage-dependent manner suggests it probable role in cancer initiation and progression. Methods: In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases. Results: Here, we demonstrated that SAE1 is overexpressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA-LIHC patients (n=421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and NEDD4. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n =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. Conclusion: In conclusion, the present study demonstrates that SAE1 is a targetable molecular biomarker with high potential diagnostic and prognostic implications for patients with HCC.

The expression and prognostic value of REXO4 in hepatocellular carcinoma

“…Probably one of the most frequently occurring types of cancer is HCC and its prevalence has continued to rise in recent years (21). A series of steps are involved in the development of cancer cells which involve changes in growth, cell metabolism, proliferation, and adhesion (22,23). Several studies have provided information about the biomarker of liver cancer (24,25).…”

Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

“…92-95 Others are involved in cellular senescence, apoptosis, angiogenesis, inflammation, and wound healing (LBR, EML2, SAE1). 96-99 Some of these genes (i.e., CAMK1D, TJP3, GAS8, and PDIA5) are associated with epithelial-mesenchymal transition (EMT), immune cells infiltration, and immune evasion. 100,101…”

“…[92][93][94][95] Others are involved in cellular senescence, apoptosis, angiogenesis, inflammation, and wound healing (LBR, EML2, SAE1). [96][97][98][99] Some of these genes (i.e., CAMK1D, TJP3, GAS8, and PDIA5) are associated with epithelial-mesenchymal transition (EMT), immune cells infiltration, and immune evasion. 100,101 Analysis of top KEGG pathways also indicated an upregulation of Leukocyte transendothelial migration, endocytosis (phagocytosis), neutrophil extracellular traps signaling (cellular death) pathways, and downregulation of pathways like viral carcinogenesis and drug metabolism, suggesting an MMR-induced activation of inflammation, innate and adaptive immune responses (Supplementary Fig.…”

Depletion of MRPL35 inhibits gastric carcinoma cell proliferation by regulating downstream signaling proteins

“…Immunohistochemistry (IHC) staining was performed on the tissue microarray (TMA)[ 17 , 18 ]. The method of staining is immunohistochemical streptavidin-peroxidase (SP) method.…”