Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma

被引：14
作者：
Cai, Diankui [1 ,2 ]
Yuan, Xiaoqing [1 ]
Cai, D. Q. [2 ,3 ,4 ]
Li, Ang [2 ]
Yang, Sijia [2 ]
Yang, Weibang [5 ]
Duan, Jinxin [2 ]
Zhuo, Wenfeng [2 ,6 ]
Min, Jun [1 ,2 ]
Peng, Li [1 ]
Wei, Jinxing [1 ,2 ]
机构：
[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangdong Hong Kong Joint Lab RNA Med, Guangzhou 510120, Peoples R China
[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou 510120, Peoples R China
[3] Guangdong Cardiovasc Inst, Guangzhou 510080, Peoples R China
[4] Guangdong Acad Med Sci, Guangdong Gen Hosp, Gen Surg Dept, Guangzhou 510100, Peoples R China
[5] Guangzhou Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 2, Guangzhou 510260, Peoples R China
[6] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Hepatobiliary Surg, Zhuhai 519000, Peoples R China
来源：
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2023年 / 149卷 / 13期
基金：
中国国家自然科学基金;
关键词：
Lactylation; Hepatocellular carcinoma; Immune; Prognosis; HISTONE DEACETYLASES; EXPRESSION; LACTATE; P300;
D O I：
10.1007/s00432-023-04947-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
BackgroundLactylation has been found to involve in regulating many types of biological process in cancers. However, research on lactylation-related genes in predicting the prognosis of hepatocellular carcinoma (HCC) remains limited.MethodsThe differential expression of lactylation-related genes (EP300 and HDAC1-3) in pan-cancer were examined in public databases. HCC patient tissues were obtained for mRNA expression and lactylation level detection by RT-qPCR and western blotting. Transwell migration assay, CCK-8 assay, EDU staining assay and RNA-seq were performed to verify the potential function and mechanisms in HCC cell lines after lactylation inhibitor apicidin treatment. lmmuCellAI, quantiSeq, xCell, TIMER and CIBERSOR were used to analyze the correlation between transcription levels of lactylation-related genes and immune cell infiltration in HCC. Risk model of lactylation-related genes was constructed by LASSO regression analysis, and prediction effect of the model was evaluated.ResultThe mRNA levels of lactylation-related genes and lactylation levels were higher in HCC tissues than normal samples. The lactylation levels, cell migration, and proliferation ability of HCC cell lines were suppressed after apicidin treatment. The dysregulation of EP300 and HDAC1-3 was associated with proportion of immune cell infiltration, especially B cell. Upregulation of HDAC1 and HDAC2 was closely associated with poorer prognosis. Finally, a novel risk model, based on HDAC1 and HDAC2, was developed for prognosis prediction in HCC.ConclusionHDAC1 and HDAC2 are expected to become new biomarkers for HCC. Risk scoring model based on HDAC1 and HDAC2 can be used to predict the prognosis of HCC patients.
引用
收藏
页码：11517 / 11530
页数：14
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