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RNA processing modification mediated subtypes illustrate the distinctive features of tumor microenvironment in hepatocellular carcinoma

Genes & Immunity volume 25, pages 132–148 (2024)Cite this article

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Abstract

Multiple transcript isoforms of genes can be formed by processing and modifying the 5′ and 3′ ends of RNA. Herein, the aim of this study is to uncover the characteristics of RNA processing modification (RPM) in hepatocellular carcinoma (HCC), and to identify novel biomarkers and potential targets for treatment. Firstly, integrated bioinformatics analysis was carried out to identify risk prognostic RPM regulators (RPMRs). Then, we used these RPMRs to identify subtypes of HCC and explore differences in immune microenvironment and cellular function improvement pathways between the sub-types. Finally, we used the principal component analysis algorithms to estimate RPMscore, which were applied to 5 cohorts. Lower RPMscore among patients correlated with a declined survival rate, increased immune infiltration, and raised expression of immune checkpoints, aligning with the “immunity tidal model theory”. The RPMscore exhibited robust, which was validated in multiple datasets. Mechanistically, low RPMscore can create an immunosuppressive microenvironment in HCC by manipulating tumor-associated macrophages. Preclinically, patients with high RPMscore might benefit from immunotherapy. The RPMscore is helpful in clustering HCC patients with distinct prognosis and immunotherapy. Our RPMscore model can help clinicians to select personalized therapy for HCC patients, and RPMscore may act a part in the development of HCC.

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Fig. 1: Identification of differential expression and prognostic of RPMRs in TCGA-LIHC.
Fig. 2: The molecular subtypes categorization of HCC base on 8 RPMRs.
Fig. 3: Identification of gene subtypes based on 86 prognostic RPMRs-related DEGs.
Fig. 4: Construction of RPMscore.
Fig. 5: Low RPMscore create an immunosuppressive microenvironment in HCC.
Fig. 6: Low RPMscore conferred attenuated antitumor immunity through macrophages chemotaxis.
Fig. 7: The prognostic value of RPMscore in HCC patients.
Fig. 8: Internal and external validation of RPMscore.
Fig. 9: RPMscore in the role of anti-PD-1/L1 immunotherapy.
Fig. 10
Fig. 11: RPMscore is a robust independent prognosis factor in Fudan cohort.

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Data availability

The datasets generated for this study can be found in the GEO database (GSE14520, GSE36376, GSE76427, GSE20140, GSE27150, GSE140901; https://www.ncbi.nlm.nih.gov/geo/), and UCSC Xena website (https://gdc.xenahubs.net).

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Funding

This research was supported by the Construction of Major Subject [Grant no. (YNZDXK202201, 2022-2025)] of Huadu District People´s Hospital of Guangzhou; the construction project of inheritance studio of national famous and old traditional Chinese Medicine experts (Grant no.140000020132).

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Author notes

  1. These authors contributed equally: Xinhui Li, Shan Liu, Laibin Zou.

Authors and Affiliations

  1. Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, PR China

    Xinhui Li & Shan Liu

  2. Department of Hepatobiliary and Pancreatic Surgery, Huadu District People´s Hospital of Guangzhou, The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510800, China

    Laibin Zou

  3. Department of Traditional Chinese Medicine and Allergy, The third affiliated hospital of Sun Yet-sen University, Guangzhou, 510800, China

    Min Dai

  4. Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, PR China

    Chaobei Zhu

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Contributions

M.D. and X.H.L. conceived the project. S.L. acquired and processed raw sequencing data. L.B.Z. performed data integration and conducted data analysis. X.H.L. and S.L. assisted in the interpretation of results. C.B.Z. wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Min Dai or Chaobei Zhu.

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The study was approved by the ethical committee in the Renmin Hospital, Hubei University of Medicine, and conducted under the guidance of the Declaration of Helsinki.

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Li, X., Liu, S., Zou, L. et al. RNA processing modification mediated subtypes illustrate the distinctive features of tumor microenvironment in hepatocellular carcinoma. Genes Immun 25, 132–148 (2024). https://doi.org/10.1038/s41435-024-00265-8

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