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The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity

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Abstract

Background

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity.

Methods

Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite).

Results

Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes.

Conclusion

We identified 14 MRP genes as HCC diagnostic markers. We investigated FRG and m6A modification-related gene expression profiles and immune features in patients with HCC, and developed and validated a model incorporating MRP and FRG expression that accurately and reliably predicts HCC prognosis and may predict disease progression and treatment response.

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All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Acknowledgements

The authors would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

Funding

This work was supported by The National Key Research and Development Program of China (2021YFC2600200), the National Nature Science Foundation of China (No. 81801972), Science and Technology Research Project of Jilin Provincial Department of Education (JKH20211179KJ; 2016444), and the Jilin Provincial Nature Science Foundation of Jilin Provincial Department of Science and Technology (20200201544JC; 20210101341JC).

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Authors and Affiliations

  1. Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China

    Jin-Wei Zhao, Xin-Hua Cui, Lin Xing, Jia-Cheng Shi & Lu Yu

  2. Medical College of YanBian University, YanBian, 133000, China

    Wei-Yi Zhao

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  1. Jin-Wei Zhao
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Contributions

Conception and design of the research: ZJW and YL. Acquisition of data: CXH, ZWY, and XL. Analysis and interpretation of the data: ZWY and XL. Statistical analysis: XL, SJC, and CXH. Obtaining financing: ZJW and YL. Writing of the manuscript: ZJW and ZWY. Critical revision of the manuscript for intellectual content: ZJW and YL. All authors read and approved the final draft.

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Correspondence to Lu Yu.

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Zhao, JW., Zhao, WY., Cui, XH. et al. The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity. Clin Transl Oncol 26, 496–514 (2024). https://doi.org/10.1007/s12094-023-03269-4

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