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

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Abstract

Background

Lactylation 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.

Methods

The 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.

Result

The 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.

Conclusion

HDAC1 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.

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Data availability statement

The original contributions presented in the study are included in the article.

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Funding

This work was supported by the national natural science foundation of China (Grant Numbers: 81672420, 81702406) and the Natural Science Foundation of Guangdong Province of China (2016A030310207).

Author information

Author notes

  1. Diankui Cai, Xiaoqing Yuan and D. Q. Cai have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Diankui Cai, Xiaoqing Yuan, Jun Min, Li Peng & Jinxing Wei

  2. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Diankui Cai, D. Q. Cai, Ang Li, Sijia Yang, Jinxin Duan, Wenfeng Zhuo, Jun Min & Jinxing Wei

  3. Guangdong Cardiovascular Institute, Guangzhou, 510080, China

    D. Q. Cai

  4. General Surgery Department, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510100, China

    D. Q. Cai

  5. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Weibang Yang

  6. Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China

    Wenfeng Zhuo

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  1. Diankui Cai
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Contributions

DC, XY and DQC collected data and analyzed data. DC and DQC wrote the manuscript. DC, XY, DQC, JW, AL, SY, WY, JD and WZ checked and amend manuscript. LP and JM designed the research.

Corresponding authors

Correspondence to Jun Min, Li Peng or Jinxing Wei.

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The authors have not disclosed any competing interests.

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Scheme of this research was approved by the Institutional Research Ethics Committee of the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Guangzhou, China).

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Cai, D., Yuan, X., Cai, D.Q. et al. Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma. J Cancer Res Clin Oncol 149, 11517–11530 (2023). https://doi.org/10.1007/s00432-023-04947-0

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