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Whole-transcriptome and proteome analyses identify key differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs associated with HCC

Oncogene volume 40, pages 4820–4831 (2021)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. To gain more insights into the transcriptomic landscape and molecular mechanism of HCC, we performed TMT-labelled tandem mass spectrometry (n = 4) and whole-transcriptome sequencing (n = 3) based on HCC tumour (T) and adjacent normal (N) tissues from seven HCC patients. To comprehensively evaluate the gene-regulatory circuits in HCC, differential expression and enrichment analyses were performed on the differentially expressed proteins (DEPs), genes (DEGs), miRNAs (555), lncRNAs (29) and circRNAs (895). A total of 977 proteins and 243 genes were found to be differentially expressed in HCC tumours compared with adjacent normal tissues. HCC data from The Cancer Genome Atlas were used to validate the results. Combined with the results above, 56 DEP-DEGs with common changes in relative quantity were identified. Functional pathway analysis showed that the DEP-DEGs were mainly enriched in the spliceosome and various metabolic processes. Bioinformatics analysis showed that hsa-miR-1266-5p, hsa-miR-128-1-5p, hsa-miR-139-5p, hsa-miR-34b-3p and hsa-miR-570-3p were involved in the regulation of the hub genes mentioned above. The crucial coexpression (lncRNA–mRNA, circRNA–mRNA) and competing endogenous RNA interaction axes showed the possible functions of the lncRNAs and circRNAs. We explored potential cancer biomarkers by combining proteomic and transcriptomic studies. Our study provides a valuable resource for understanding regulatory mechanisms at the RNA level and may ultimately further assist in the development of diagnostic and/or therapeutic targets for HCC.

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Fig. 1: Flowchart of the study design.
Fig. 2: Expression pattern of differently expressed proteins and RNAs between the HCC and the adjacent normal group.
Fig. 3: Enrichment analysis of miRNA, lncRNA target genes and circRNA parent genes.
Fig. 4: Enrichment analysis of DEP-DEGs.
Fig. 5: Correlation analysis of proteome and transcriptome in HCC tumour and adjacent normal tissues.
Fig. 6: Enrichment analysis of differential proteins/genes (DEP-DEGs) between proteome and transcriptome in HCC tissues.
Fig. 7: Network of lncRNAs, mRNAs and miRNAs.
Fig. 8: The expression level and overall survival of typical differential expressed proteins in HCC.

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Data availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://www.ebi.ac.uk/pride/archive/) via the PRIDE partner repository with the dataset identifier PXD014915. The RNA-Seq datasets have been uploaded to The National Omics Data Encyclopedia (https://www.biosino.org/node/) with the accession number OEP001672.

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Acknowledgements

We gratefully acknowledge Henan Key Laboratory of Pharmacology for Liver Diseases for providing experimental platform support. We thank Dr. Jianxiang Shi for assistance in bioinformatic analysis. This work was supported by grants from Natural Science Foundation of Henan Province (No. 182300410361); the Major Project of Science and Technology in Henan Province (No. 161100311400); the National Science and Technology Major Project of China (No. 2018ZX10302205); Project of Basic Research Fund of Henan Institute of Medical and Pharmacological Sciences (No. 2020BP0107; No. 2020BP0111); Zhengzhou Major Project for Collaborative Innovation (18XTZX12007) and The Key Scientific and Technological Project of Henan Province (No. 212102310124).

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Authors and Affiliations

  1. Henan Institute of Medical and Pharmaceutical Sciences & BGI College, Zhengzhou University, Zhengzhou, China

    Fang Xu, Liya Jiang, Qianwei Zhao, Yixian Liu, Shuangshuang Yang, Huiping Chen, Jianying Zhang & Jintao Zhang

  2. School of Life Sciences, Zhengzhou University, Zhengzhou, China

    Liya Jiang & Zhibiao Zhang

  3. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China

    Mengdan Yu

  4. Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, China

    Jianying Zhang & Jintao Zhang

  5. State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China

    Jianying Zhang & Jintao Zhang

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Xu, F., Jiang, L., Zhao, Q. et al. Whole-transcriptome and proteome analyses identify key differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs associated with HCC. Oncogene 40, 4820–4831 (2021). https://doi.org/10.1038/s41388-021-01908-0

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