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Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer

  • Authors:
    • Zhenshan Zhang
    • Jun Sun
    • Chao Jin
    • Likun Zhang
    • Leilei Wu
    • Gendong Tian
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China, Department of Ocean, Shandong University, Weihai, Shandong 264209, P.R. China, Department of Clinical Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161003, P.R. China, Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 457
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    Published online on: September 6, 2023
       https://doi.org/10.3892/ol.2023.14044
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Abstract

Metastasis is a fatal status for liver cancer, and the identification of an effective prediction model and promising therapeutic target is essential. Given the known relationship between fatty acid (FA) metabolism and the liver, the present study aimed to investigate dysregulation of genes associated with FA metabolism in liver cancer. Bioinformatics analyses were performed on data from patients with hepatocellular carcinoma (HCC) obtained from The Cancer Genome Atlas database using R software packages. Online public tools such as the Human Protein Atlas, Tumor Immune Single‑Cell Hub and the University of Alabama at Birmingham Cancer Data Analysis portal were also utilized. Some essential results were further verified using in vitro experiments using HepG2 liver cancer cells. A signature consisting of three genes associated with the progression and prognosis of HCC and FA metabolism was identified. When samples were scored based on the expression of these genes and divided according to the median value, the higher score group showed a worse outcome and repressive immune microenvironment than the lower score group. Downstream pathways such as hypoxia, IL6/JAK/STAT3 and epithelial‑mesenchymal transition were found to be significantly activated in the higher score group. As the core factor in the signature, mitochondrial ribosomal protein L35 (MRPL35) was found to be upregulated in HCC and to have certain impacts on the dysregulation of effective immunity. Further investigations and in vitro experiments indicated that MRPL35 facilitates the migration and invasion abilities of liver cancer, and the resistance of HCC to treatment. These findings have important implications regarding the characteristics and mechanisms of metastasis in liver cancer, and provide a promising signature based on FA metabolism‑related genes that may be used to predict outcomes and explored as a novel therapeutic target in liver cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Sun J, Jin C, Zhang L, Wu L and Tian G: Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer. Oncol Lett 26: 457, 2023.
APA
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., & Tian, G. (2023). Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer. Oncology Letters, 26, 457. https://doi.org/10.3892/ol.2023.14044
MLA
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., Tian, G."Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer". Oncology Letters 26.4 (2023): 457.
Chicago
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., Tian, G."Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer". Oncology Letters 26, no. 4 (2023): 457. https://doi.org/10.3892/ol.2023.14044
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Z, Sun J, Jin C, Zhang L, Wu L and Tian G: Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer. Oncol Lett 26: 457, 2023.
APA
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., & Tian, G. (2023). Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer. Oncology Letters, 26, 457. https://doi.org/10.3892/ol.2023.14044
MLA
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., Tian, G."Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer". Oncology Letters 26.4 (2023): 457.
Chicago
Zhang, Z., Sun, J., Jin, C., Zhang, L., Wu, L., Tian, G."Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer". Oncology Letters 26, no. 4 (2023): 457. https://doi.org/10.3892/ol.2023.14044
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