1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
2. Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, 530021, Nanning, People's Republic of China.
3. Key Laboratory of early Prevention & Treatment for regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
#Haixiang Xie and Kejian Yang contribute equally to this work.
This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.
Keywords: Hepatocellular carcinoma, Sarcosine dehydrogenase, Biomarkers, Immune infiltration, Prognostic