Identification and Validation of Nicotinamide Metabolism-Related Gene Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma

Abstract

Sijia Yang,1,2,* Ang Li,1,2,* Lihong Lv,3,* Jinxin Duan,2 Zhihua Zheng,4 Wenfeng Zhuo,5 Jun Min,2 Jinxing Wei2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, People’s Republic of China; 2Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Clinical Trial Institution of Pharmaceuticals, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangdong Province Engineering Laboratory for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, People’s Republic of China; 5Department of Hepatobiliary Surgery, the Fifth Affiliated Hospital, Sun Yat-sen University 528406 Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinxing Wei; Jun Min, Email [email protected]; [email protected]: Nicotinamide (NAM+) regulates redox and metabolic activities in the mitochondria. The intention of the research was to identify key genes that relate to nicotinamide in hepatocellular carcinoma (HCC).Methods: Relevant clinical information were collected as well as RNA-seq data using the Cancer Genome Atlas (TCGA) database. Differential analysis was used to discover the genes that were differently expressed. On the key genes associated with NAM, functional enrichment analysis was carried out. Next, receiver operating characteristic (ROC) and prognosis Kaplan-Meier (K-M) curve analyses were used to evaluate the importance of important gene expression, respectively. The immune cell signatures were estimated using the CIBERSORT algorithm. Finally, the anticancer impact of NAM on HCC was experimentally confirmed, and important genes NADSYN1 and NT5C were validated at the protein level in clinical specimens.Results: Six prognostic key genes (NAXE, NADSYN1, NT5C, NT5C3A, PNP and NT5E) were identified. There is an association between the level of key gene expression and the clinical prognosis. Four key genes (NAXE, NADSYN1, NT5C and NT5C3A) have statistical significance of survival prognosis. Finally, the expression of NAM-related genes and the inhibitory effect of NAM on HCC were verified by experiments.Conclusion: The study first found some Nicotinamide metabolism-related differentially expressed genes (NMRDEGs) that are related to HCC can contribute to predicting survival and monitoring the treatment.Keywords: hepatocellular carcinoma, nicotinamide, bioinformatics analysis, diagnostic, prognostic

Keywords

• hepatocellular carcinoma
• nicotinamide
• bioinformatics analysis
• diagnostic
• prognostic