Abstract

ADAM15 is highly expressed in malignant tumors and is correlated with tumor progression. However, the role of ADAM15 in hepatocellular carcinoma (HCC) remains unclear. In the study, our results indicated that ADAM15 was highly expressed in HCC tissues and cells compared with corresponding tissues and liver cells. Overexpression of ADAM15 was linked to poor prognosis, and was an independent risk factor for HCC prognosis. Besides, analysis of immune infiltration indicated that ADAM15 expression was related to tumor infiltrating lymphocytes based on the TIMER, TISIDB and GEPIA databases. Many immune checkpoint gene expression was associated with ADAM15 expression. Functional enrichment analyses indicated that apoptosis, cell adhesion was enriched. ADAM15 knockdown promoted apoptosis and suppressed proliferation, migration and invasion of liver cancer cells. The findings of western blot showed that ADAM15 knockdown reduced the expression of Bcl-2, Vimentin, N-Cadherin and Snail, and elevated the expression of Bax, E-cadherin and ZO-1. However, overexpression of ADAM15 had the opposite results. Collectively, our findings demonstrated that ADAM15 was connected with poor prognosis of HCC patients, and could be considered as a potential biomarker for the diagnosis and treatment of HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is the major histological type of primary liver cancer, and is a big health care burden in the world [1]

  • We further confirmed that ADAM15 was up-regulated in HCC tissues compared with corresponding noncancerous tissues based on the analysis of RT-qPCR, Western blot and Immunohistochemical staining (IHC)

  • The level of ADAM15 expression was higher in HCC samples than that in adjacent noncancerous samples based on the TCGA and GEO analyses, and overexpression of ADAM15 came with worse overall survival (OS) and recurrence-free survival (RFS)

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the major histological type of primary liver cancer, and is a big health care burden in the world [1]. There are many ways for HCC treatment, including surgical resection, local ablation therapy, transplantation, transcatheter arterial chemoembolization, and targeted treatment [3,4,5,6], the main treatment for early-stage HCC is hepatectomy. Due to many patients are diagnosed at the late stage of HCC, the majority of them lose the opportunity for radical surgical treatment, the 5-year survival rate of patients with advanced HCC after surgical intervention remains less than 18% [7]. It’s urgent for us to explore novel markers for early diagnosis and treatment of HCC

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