Expressions of YTH family members in hepatocellular carcinoma and their prognostic values
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1.Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China;2.Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China

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R735.7

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    Abstract:

    Background and Aims All the YTH family members belong to the m6A reading protein, and are involved in the regulation of methylation in tumor development. However, the expression and specific role of the YTH family in hepatocellular carcinoma (HCC) remains to be further elucidated. Therefore, this study was conducted to explore the expression profiles and prognostic value of YTH family members and their relations with immune infiltration and relevant functions based on bioinformatics approaches.Methods The expression profiles of YTH family members in HCC and its subgroups were analyzed using UALCAN database, and their prognostic value in HCC were evaluated using Kaplan-Meier plotter. The co-expression profiles and genetic alterations of YTH family members were analyzed using the cBioPortal. The function and pathway enrichment analysis of YTH family were performed using WebGestalt database. The correlation analysis of YTH family and immune cell infiltration in HCC was conducted using TIMER 2.0 database.Results The mRNA expression levels of YTHDC1, YTHDC2, YTHDF1, YTHDF2 and YTHDF3 in HCC were significantly increased compared with those in normal liver tissues, and were closely related to clinical TNM stage and tumor grade, and their mRNA expression levels were progressively increased in 1, 2 and 3 stage/grade, while decreased in 4 stage/grade. Prognostic analysis showed that high expressions of both YTHDF1 and YTHDF2 were significantly associated with shorter overall survival (OS) and relapse-free survival (RFS). Analysis of the TCGA database and cBioPortal showed that the genetic alteration rate of YTHDF3 was 25%, which was the highest among YTH family members. GO function enrichment analysis showed that the main functions of YTH family were oriented toward metabolism and biosynthesis decomposition, especially hormone metabolism, sterol metabolism, lipid metabolism, drug catabolism, etc. The TIMER 2.0 database analysis showed that the expressions of most YTH family members were significantly positively correlated with the infiltration of CD4+ T cells, CD8+ T cells, B cells, neutrophils and dendritic cells, and negatively correlated with the infiltration of macrophages.Conclusion The molecular and expression profiles of YTH members were dysregulated in HCC. YTH family members (especially YTHDF1 and YTHDF2) are potential prognostic markers and new therapeutic targets. These findings may provide a new avenue for studying the mechanism and targeted therapy of HCC.

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HU Kuan, YAO Lei, LI Juanni. Expressions of YTH family members in hepatocellular carcinoma and their prognostic values[J]. Chin J Gen Surg,2021,30(7):836-846.
DOI:10.7659/j. issn.1005-6947.2021.07.010

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History
  • Received:May 05,2021
  • Revised:June 26,2021
  • Adopted:
  • Online: August 25,2021
  • Published: