Abstract

Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and mortality worldwide. lysine acetylation regulators (LARs) dynamically regulate Lysine acetylation modification which plays an important regulatory role in cancer. Therefore, we aimed to explore the potential clinical prognostic value of LARs in HCC. Methods: Differentially expressed LARs in normal liver and HCC tissues were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To identify genes with prognostic value and establish the risk characteristics of LARs, consensus clustering was employed. We used univariate Cox regression survival analysis and LASSO Cox regression based on LARs to determine the independent prognostic signature of HCC. CIBERSORT and Gene Set Enrichment Analysis (GSEA) were used to estimate immune infiltration and functional enrichment analysis respectively. The expression of LAR was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). statistical analyses were conducted using SPSS and R software. Results: In this study, the 33 LARs expression data and corresponding clinical information of HCC were obtained using TCGA and ICGC datasets. We found majority of the LARs were differentially expressed. Consensus cluster analysis was carried out based on the TCGA cohort, and three HCC subtypes (cluster 1, 2, and 3) were obtained. The LA3 subgroup had the worst clinical outcomes. Nine key LARs were identified to affect prognosis. The results showed that LARs signature has a strong independent prognostic value in HCC patients, whether in the training datasets or in the testing datasets. GSEA results showed that various tumor-related processes and pathways were abundant in the high-risk groups. RT-qPCR results showed that HAT1, HDAC1, HDAC2, HDAC4, and HDAC11 were highly expressed in HCC cells. Conclusion: Our results suggest that LARs play critical roles in HCC and are helpful for individual prognosis monitoring and clinical decision-making of HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, ranking sixth in cancer incidence and fourth in mortality worldwide (Kulik and El-Serag, 2019; Huang et al, 2021)

  • The results showed that lysine acetylation regulators (LARs) signature has a strong independent prognostic value in HCC patients, whether in the training datasets or in the testing datasets

  • Our results suggest that LARs play critical roles in HCC and are helpful for individual prognosis monitoring and clinical decision-making of HCC

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, ranking sixth in cancer incidence and fourth in mortality worldwide (Kulik and El-Serag, 2019; Huang et al, 2021). Post-translational modification (PTM) is an important way to regulate protein function and affect cell behavior, and act as a signal marker in cancer cells (Chen et al, 2020; Figlia et al, 2020). Lysine acetylation is an important reversible and dynamic protein PTM that is exceedingly important for gene expression. It plays an important role in transcription factor activity, chromatin remodeling, and metabolic enzyme activity, and is related to tumorigenesis, tumor progression, and metastasis (Choudhary et al, 2014; Kaypee et al, 2016; Narita et al, 2019). We systematically studied the role of LARs in HCC in order to provide potential prognostic markers and therapeutic targets. Lysine acetylation regulators (LARs) dynamically regulate Lysine acetylation modification which plays an important regulatory role in cancer. We aimed to explore the potential clinical prognostic value of LARs in HCC

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