Transcriptomic analysis reveals prognostic molecular subtype and candidate risk model for pseudouridylation- related genes in hepatocellular carcinoma

Author:

Lan Chenlu1,Wei Yongguang1,Huang Huasheng1,Qin Haifei1,Huang Ketuan1,Zhou Xin1,Yang Chengkun1,Liao Xiwen1,Zhu Guangzhi1,Peng Tao1

Affiliation:

1. The First Affiliated Hospital of Guangxi Medical University

Abstract

Abstract

Growing studies have shown pseudouridylation can regulate translation and gene expression, but the molecular characteristics of pseudouridylation remain unknown in hepatocellular carcinoma (HCC). Based on public databases, we identified pseudouridylation-related molecular cluster and risk score model to evaluate the prognosis, clinical characteristic, molecular mechanisms, immune landscape of HCC. Polymerase Chain Reaction (PCR) was adopted to verify the expression of RDM1, CDCA3 and FLVCR1. We found that pseudouridylation-related genes (PRGs) mainly participate in regulation of transcription and translation. The prognostic PRGs can divide HCC sample into two subtypes, the cluster1 characterized with high AFP, poor differentiation, advanced tumor stage, large tumor size, frequent TP53 mutation, up-regulation of cell cycle and mitosis, and poor prognosis, which was similar to the proliferation type of HCC. On the contrary, the cluster2 presented good prognosis and increased infiltration of immune cells, which was partly similar to the non-proliferation HCC and may benefit from immunotherapy. Furthermore, the risk score model, constructed by RDM1, CDCA3 and FLVCR1, was demonstrated to be significantly related to prognosis, and be an independent prognostic factor. The overall survival (OS) and recurrence free survival (RFS) of high-risk group were worse than the low-risk. Receiver operating characteristic (ROC) curve revealed the model had a better predictive performance for 1- and 3- year survival with the maximum AUC reached 0.806. Functional enrichment analysis suggested that gene sets of cell cycle-, mitotic division-related biological processes and cell signaling pathways were upregulated in high-risk group, such as PLK1 pathway, FOXM1 pathway, P53 regulation pathway and so on. PCR experiment discovered the expression of RDM1, CDCA3 and FLVCR1 were obviously overexpressed in HCC tissues, which was consistent with public data. In conclusion, the prognostic PRGs related-molecular subtype and risk model may effectively forecast the prognosis and immune landscape of HCC.

Publisher

Springer Science and Business Media LLC

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