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The  SCN  family as the encoded gens of sodium channels has been proven to participate in development of cancers including hepatocellular carcinoma (HCC), but the prognostic value of the  SCN  family is unclear. The results of the UALCAN database had showed that  SCN2A/4A/5A/8A  mRNA were highly expressed in tumour tissues, while  SCN1A/7A/11A  mRNA were expressed at low levels ( p  &amp;lt; 0.05), furthermore, the expression of  SCN4A  and  SCN7A  had the similar levels in microarray analysis result. The pan-tumour analysis showed that  SCN7A  expression was stably lower in tumours than  SCN4A  expression by TIMER. Both  SCN4A  and  SCN7A  were related to tumour grade, nodal metastatic status, histological subtype, patient race, individual cancer stages and TP53 mutation status to varying degrees. The Kaplan–Meier plotter demonstrated that high  SCN4A  mRNA expression was correlated with better overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) and that high expression of  SCN7A  mRNA was associated with better OS; however, in Asians, higher  SCN4A  was correlated with better OS and DSS, and higher  SCN7A  was well correlated with better OS, recurrence-free survival (RFS), DSS and PFS. Analysis of data from cBioPortal showed that mutation of  SCN7A  was related to RFS and PFS. The protein expression of  SCN4A  and  SCN7A  had been detected by Immunohistochemistry. Univariate survival analysis revealed that high  SCN7A  protein expression was significantly linked to better OS ( p  = 0.001) and RFS ( p  = 0.003). Moreover,  SCN7A  displayed as an independent prognostic factor by multivariate analysis. In addition, a lower methylation level indicated a poor outcome. Pathway and functional enrichment analysis predicted a relationship between  SCN7A  and the PI3K pathway. In conclusion, there are significant and stable changes in  SCN4A  and  SCN7A  expression in HCC.  SCN7A  expression has better prognostic value and might participate in HCC progression.

Comprehensive Analysis to Identify the Encoded Gens of Sodium Channels as a Prognostic Biomarker in Hepatocellular Carcinoma