Comprehensive Bioinformatics Analysis For Prognostic Implication Of The SLC16A Gene Family In Hepatocellular Carcinoma

Background Liver cancer is still challenging for global health at present.In recent years,the incidence of liver cancer has dramatically increased worldwide,and it has a high mortality rate.Hepatocellular carcinoma(HCC)accounts for approximately 90% of primary liver cancer cases.Considerable efforts have been made to define possible mechanisms implicated in the development,progression,and metastasis of HCC,leading to a broad diversity of therapeutics for HCC.However,the molecular mechanism underlying the occurrence and progression of HCC has been poorly addressed,and the prognosis of HCC patients continues to be gloomy.Increasing the understanding of the potential genetic pathogenesis for HCC will contribute to the development of diagnostic and prognostic biomarkers as well as the identification of potential therapeutic targets.The solute carriers family 16(SLC16As)plays a crucial role in tumorigenesis and progression.However,the explicit effects of 14 individual SLC16 members on tumorigenesis and progression of HCC remain unclear.Objective: In this study,we analyzed the m RNA expression of different SLC16 As family members in HCC and their relationship with clinical parameters in HCC patients,and analyzed their potential as a prognostic marker in HCC patients.Then,we analyzed SLC16 As mutations and their effects on the prognosis of HCC patients,predicted the interactions between SLC16 As family proteins,and finally predicted the functions and pathways of SLC16 As and its 280 similar genes.Methods: We compared the m RNA expression of 14 SLC16 As between HCC and normal liver samples with Oncomine datasets as well as validated the differential expression with ULCAN.The overall survival(OS)of the HCC patients was compared between the high-and low-expression groups using Kaplan–Meier analysis.Multivariate Cox regression evaluated the independent prognostic value of the 14 SLC16 A m RNAs after adjusting for clinicopathological features.Biological functions and signaling pathways that were related to SLC16 As and their coexpressed genes in HCC were interrogated by function enrichment and pathway analysis.Results: The m RNA expression levels of SLC16A3,4,11,and 14 were verified to be differentially expressed by both Oncomine and ULCAN.Kaplan–Meier analysis determined a correlation between HCC prognosis and the m RNA expression of SLC16A2,3,4,7,and 11.Multivariate regression identified a higher expression of SLC16A3 as well as a lower expression of SLC16A4 and SLC16A11 as independent risk factors for HCC mortality.The biological functions of the 14 SLC16 As and their 280 coexpressed genes were primarily enriched in monocarboxylate transporter(MCT)activity.Conclusion: Our bioinformatics findings suggest that SLC16A3,SLC16A4,and SLC16A11 m RNA can be promising prognostic biomarkers and potential therapeutic targets for HCC,but their diagnostic efficacy will not be guaranteed until well-designed clinical trials and laboratory studies are completed in the future.