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

Jiangning Gu; Shiqi Xu; Xiang Chen; Haifeng Luo; Guang Tan; Wenjing Qi; Feng Ling; Chenqi Wang; Feiliyan Maimaiti; Yunlong Chen; Lili Yang; Menghong Yin; Dan Chen

doi:10.17305/bjbms.2022.7268

Authors

Jiangning Gu Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0002-9258-9881
Shiqi Xu Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0002-1736-2708
Xiang Chen Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0003-3691-7155
Haifeng Luo Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0003-3519-7408
Guang Tan Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China
Wenjing Qi Department of Pathology, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0001-9256-2358
Feng Ling Department of Nursing, The First affiliated Hospital of Dalian Medical University, Dalian, China https://orcid.org/0000-0002-7579-367X
Chenqi Wang Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0001-6907-5025
Feiliyan Maimaiti Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0002-7579-367X
Yunlong Chen Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China
Lili Yang Department of Hepatobiliary Surgery, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0003-0667-085X
Menghong Yin Department of Sports Medicine, Dalian Municipal Central Hospital, Dalian Medical University, Dalian, Liaoning Province, China
Dan Chen Department of Pathology, the First affiliated hospital of Dalian Medical University, Dalian, Liaoning Province, China https://orcid.org/0000-0001-6795-1837

DOI:

https://doi.org/10.17305/bjbms.2022.7268

Keywords:

ORM1, microvascular invasion, sorafenib sensitivity, 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 via integrative analysis of Gene Express Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The protein expression level of ORM1 in our cohort was determined using 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 to that in the non-cancerous cells. However, it was upregulated in microvascular invasion samples, especially in the cancer embolus compared to that in the surrounding tumor cells. Though Kaplan-Meier analysis did not show an association of ORM1 expression with the overall survival rates of HCC patients, 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 (EMT) alteration, which was consistent with our bioinformatic analysis. Hence, ORM1 played a key role in HCC tumorigenesis and may serve as a potential target for the development of therapeutics against HCC in the future.