Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is still a major global problem in health care systems regarding that HCC is the third leading cause of cancer-related deaths worldwide.[1]
The cut-off value of positivity for SRY-box 9 (SOX9) staining was set to 5% positive tumour cells/per 10 high-power fields (HPF)
SOX9 has been implicated as a cancer stem cell marker with the ability to drive cancer growth and promote cancers metastatic ability[25,26]
Summary
Hepatocellular carcinoma (HCC) is still a major global problem in health care systems regarding that HCC is the third leading cause of cancer-related deaths worldwide.[1]. Palliative treatment measures including sorafenib, regorafenib (multi-kinase inhibitors) and chemoembolization.[9,10] The 5-year survival rate within the first group of patients is up to 70% and the median overall survival (OS) is more than 60 months. Within five years the majority of patients (~70%) develop metastatic disease or de novo HCC.[11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
