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Construction of a m5C-related long non-coding RNA signature for the prognosis of hepatocellular carcinoma

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Abstract

RNA modification serves as a kind of posttranscriptional modification. Besides N6-methyladenosine (m6A), 5-methylcytosine(m5C) is also an important RNA modification. Long non-coding RNAs (lncRNAs) play an important role in tumor progression. Thus, we performed bioinformatic analysis to establish a m5C-related lncRNA signature(m5ClncSig) for hepatocellular carcinoma (HCC). The RNA sequencing data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation coefficient analysis was applied to conduct m5C-related genes and m5C-related lncRNAs co-expressing network. Univariate Cox regression was used to screen the m5C-related lncRNAs with prognosis value. LASSO regression was applied to establish m5ClncSig. Functional analysis including KEGG and GO were performed. The relation between m5ClncSig and immunity was assessed by CIBERSORT and ESTIMATE. RP11-498C9.15 was selected for in vitro validation. A m5ClncSig was established containing 8 lncRNAs with significantly prognosis value. According to risk score calculated by m5ClncSig, high-risk group had worse clinical outcomes than low-risk group. The risk score was validated as an independent prognosis factor. Moreover, the abundances of 11 types of immune cells were significantly different between high-risk group and low-risk group while 8 immune-related genes expressed differently between these two groups. RP11-498C9.15 was validated as a risk factor in HCC progression.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

This study was supported by the National Natural Science Foundation of China (grant number 81670595 and 81970568).

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Authors and Affiliations

Authors

Contributions

JL and JX: designed this work. JL and HW: performed the bioinformatics analysis. DC: performed the wet experiments. WC and ZH: wrote the manuscript. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Junming Xu.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by Medical Ethics Committee of Shanghai General Hospital (approved number: 2022SQ154). The patients provided their written informed consent to participate in this study.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 Table S1 202 m5C-related lncRNAs. (DOCX 20 KB)

13577_2022_845_MOESM2_ESM.docx

Supplementary file2 Table S2 368 HCC samples were divided into high-risk group and low-risk group according to the risk score. (DOCX 20 KB)

Supplementary file3 Table S3 The results of Univariate Cox regression and multivariable Cox regression (DOCX 52 KB)

Supplementary file4 (PDF 94 KB)

Supplementary file5 (PDF 93 KB)

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Lu, J., Wang, H., Cao, W. et al. Construction of a m5C-related long non-coding RNA signature for the prognosis of hepatocellular carcinoma. Human Cell 36, 712–724 (2023). https://doi.org/10.1007/s13577-022-00845-8

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  • DOI: https://doi.org/10.1007/s13577-022-00845-8

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