Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortalities worldwide. The role of ornithine transcarbamylase (OTC) in HCC remains unclear. In the present study, the expression of OTC in HCC was analyzed based on datasets from the Gene Expression Omnibus database of the National Center for Biotechnology Information and further confirmed by immunohistochemistry, western blotting analysis and reverse transcription-quantitative polymerase chain reaction assays on clinical samples and cell lines. Furthermore, the associations between OTC expression and clinicopathological parameters as well as clinical outcome, including the overall and disease-free survival rates were analyzed. Finally, the effect of OTC on HCC cells was measured using proliferation, bromodeoxyuridine and colony-formation assays. Lower OTC expression was observed in HCC cells and tissues compared with primary human hepatocytes. Further investigation demonstrated that low expression of OTC in HCC was associated with larger tumor size and advanced grade. A Kaplan-Meier analysis revealed that patients with lower levels of OTC exhibited shorter overall and disease-free survival times. Notably, OTC silencing with RNA interference facilitated cell proliferation in HCC SK-Hep-1 and Huh-7 cells. However, overexpression of OTC led to inhibition of cell proliferation. In conclusion, the present study identified a novel role of OTC in HCC development, providing a potential novel therapeutic target for this disease.