EXOSC10 is a novel hepatocellular carcinoma prognostic biomarker: a comprehensive bioinformatics analysis and experiment verification

PeerJ. 2023 Sep 8:11:e15860. doi: 10.7717/peerj.15860. eCollection 2023.

Abstract

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor. There are few studies on EXOSC10 (exosome component 10) in HCC; however, the importance of EXOSC10 for HCC remains unclear.

Methods: In the study, the prognosis value of EXOSC10 and the immune correlation were explored by bioinformatics. The expression of EXOSC10 was verified by tissue samples from clinical patients and in vitro experiment (liver cancer cell lines HepG2, MHCC97H and Huh-7; normal human liver cell line LO2). Immunohistochemistry (IHC) was used to detect EXOSC10 protein expression in clinical tissue from HCC. Huh-7 cells with siEXOSC10 were constructed using lipofectamine 3000. Cell counting kit 8 (CCK-8) and colony formation were used to test cell proliferation. The wound healing and transwell were used to analyze the cell migration capacity. Mitochondrial membrane potential, Hoechst 33342 dye, and flow cytometer were used to detect the change in cell apoptosis, respectively. Differential expression genes (DEGs) analysis and gene set enrichment analysis (GSEA) were used to investigate the potential mechanism of EXOSC10 and were verified by western blotting.

Results: EXOSC10 was highly expressed in tissues from patients with HCC and was an independent prognostic factor for overall survival (OS) in HCC. Increased expression of EXOSC10 was significantly related to histological grade, T stage, and pathological stage. Multivariate analysis indicated that the high expression level of EXOSC10 was correlated with poor overall survival (OS) in HCC. GO and GSEA analysis showed enrichment of the cell cycle and p53-related signaling pathway. Immune analysis showed that EXOSC10 expression was a significant positive correlation with immune infiltration in HCC. In vitro experiments, cell proliferation and migration were inhibited by the elimination of EXOSC10. Furthermore, the elimination of EXOSC10 induced cell apoptosis, suppressed PARP, N-cadherin and Bcl-2 protein expression levels, while increasing Bax, p21, p53, p-p53, and E-cadherin protein expression levels.

Conclusions: EXOSC10 had a predictive value for the prognosis of HCC and may regulate the progression of HCC through the p53-related signaling pathway.

Keywords: Bioinformatics analysis; EXOSC10; Experiment verification; Hepatocellular carcinoma; Prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carcinoma, Hepatocellular* / genetics
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • Humans
  • Liver Neoplasms* / genetics
  • Prognosis
  • Tumor Suppressor Protein p53

Substances

  • Tumor Suppressor Protein p53
  • Biomarkers
  • EXOSC10 protein, human
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex

Grants and funding

This study was supported by the Grant of research project on high-level talents of Youjiang Medical College for Nationalities (Grant No. YY2021SK02), the Foundation of Nanning Qingxiu District Key Research and Development Project (Grant No. 2020023), the Open Project of Guangxi key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Grant No. GXEKL202203), the Open Project Program of Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province (Grant No. MIRRLAB 21SZDSYS13), the Grant of Special Key Laboratory of Gene Detection & Therapy of Guizhou Province (Zunyi Medical University) (No. QJKH-KY [2017]007-002), the Grant of National-level Project of University Students’ Innovation and Entrepreneurship in 2022 (Grant No. 202210599005; 202210599007), the Grant of Guangxi Provincial-Level Project of University Students’ Innovation and Entrepreneurship in 2022 (Grant No. S202210599056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.