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

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.

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ORM 1 as a Biomarker of Increased Vascular Invasion and Decreased Sorafenib Sensitivity in Hepatocellular Carcinoma

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Published

2022-06-29

How to Cite

1.
Gu J, Xu S, Chen X, Luo H, Tan G, Qi W, Ling F, Wang C, Maimaiti F, Chen Y, Yang L, Yin M, Chen D. ORM 1 as a biomarker of increased vascular invasion and decreased sorafenib sensitivity in hepatocellular carcinoma. Bosn J of Basic Med Sci [Internet]. 2022Jun.29 [cited 2022Aug.18];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7268

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Section

Translational and Clinical Research