PLoS ONE (Jan 2017)

SOX9 is a proliferation and stem cell factor in hepatocellular carcinoma and possess widespread prognostic significance in different cancer types.

  • Georg Richtig,
  • Ariane Aigelsreiter,
  • Daniela Schwarzenbacher,
  • Anna Lena Ress,
  • Jan Basri Adiprasito,
  • Verena Stiegelbauer,
  • Gerald Hoefler,
  • Silvia Schauer,
  • Tobias Kiesslich,
  • Peter Kornprat,
  • Thomas Winder,
  • Florian Eisner,
  • Armin Gerger,
  • Herbert Stoeger,
  • Rudolf Stauber,
  • Carolin Lackner,
  • Martin Pichler

DOI
https://doi.org/10.1371/journal.pone.0187814
Journal volume & issue
Vol. 12, no. 11
p. e0187814

Abstract

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SOX9 has been previously shown to be involved in hepatocellular carcinoma (HCC) and other types of cancer. However, prognostic studies so far involved rather small cohorts or lack external validation and experimental data. In this study, we firstly determined the histological expression pattern of SOX9 in human HCC by immunohistochemistry (n = 84) and evaluated its prognostic value. External cohorts of publicly available datasets were used to validate its prognostic relevance in HCC (n = 359) and other types of cancer including breast (n = 3951), ovarian (n = 1306), lung (n = 1926) and gastric cancer (n = 876). Functional SOX9 knock-down studies using siRNA and cancer stem cell models were generated in a panel of liver and breast cancer cell lines. High level of SOX9 was associated with poor survival even after adjustment for other prognostic factors in multivariate analysis (HR = 2.103, 95%CI = 1.064 to 4.156, p = 0.021). SOX9 prevailed a poor prognostic factor in all cancer validation cohorts (p<0.05). Reduced SOX9 expression by siRNA decreased the growth of liver cancer cells (p<0.05). SOX9 expression was associated with stem cell features in all tested cell lines (p<0.05). In conclusion, this study demonstrated in a large number of patients from multiple cohorts that high levels of SOX9 are a consistent negative prognostic factor.