ORM 1 as a biomarker of increased vascular invasion and decreased sorafenib sensitivity in hepatocellular carcinoma

Abstract

This study aimed to clarify the role of Orosomucoid 1 (ORM1) in the development and therapy resistance in hepatocellular carcinoma (HCC). The mRNA expression level of ORM1 was analyzed through integrative analysis of Gene Express Omnibus and The Cancer Genome Atlas datasets. The protein expression level of ORM1 in our cohort was determined by immunohistochemistry. Correlation analysis was used to investigate the relationship between ORM1 expression and clinical parameters. The cell counting Kit-8 assay was used to clarify the role of ORM1 in HCC malignant behaviors, including cell growth and sorafenib sensitivity, in vitro. The results indicated that ORM1 was significantly downregulated in the hepatic cancer cells compared with the levels in non-cancerous cells; however, it was upregulated in microvascular invasion samples, especially in the cancer embolus, compared with that in the surrounding tumor cells. Although Kaplan–Meier analysis did not show an association between ORM1 expression and the overall survival rates of patients with HCC, univariate analysis indicated that ORM1 expression was highly correlated with tumor grade and stage. An in vitro assay also revealed that downregulation of ORM1 led to the suppression of tumor growth and enhancement of sorafenib sensitivity without epithelial-to-mesenchymal transition alteration, which was consistent with our bioinformatic analysis. Hence, ORM1 plays a key role in HCC tumorigenesis and may serve as a potential target for the development of therapeutics against HCC.