Catalase expression is an independent prognostic marker in liver hepatocellular carcinoma

Author:

Chen Yu-Chia1,Chen Hsin-Hung2,Chen Po-Ming34ORCID

Affiliation:

1. Department of Surgery, Division of General Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan

2. Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan

3. Research Assistant Center , Show Chwan Memorial Hospital , Changhua , Taiwan

4. Basic Medical Education Center, College of Health Sciences , Central Taiwan University of Science and Technology , Taichung , Taiwan

Abstract

Abstract Objectives Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer and originates from hepatocytes, the main functional cells of the liver. It is a serious and aggressive cancer with a generally poor prognosis, especially when diagnosed at advanced stages. Reactive oxygen species (ROS) have been detected in LIHC and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of ROS-related genes on the prognosis of LIHC. Methods Using bioinformatical tools including Gene Expression Profiling Interactive Analysis (GEPIA2) and Q-omics, a comprehensive analysis was performed to evaluate the effects of ROS-related genes, including superoxide dismutases (SODs), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs) and catalase (CAT) on the prognosis of LIHC using The Cancer Genome Atlas (TCGA) dataset and identified the most appropriate candidate genes. Then we further explored their effects on LIHC cell proliferation and drug selection for LIHC treatment. Results We found that CAT expression was significantly downregulated in late stage’s LIHC tissues compared to normal liver or early stage’s LIHC tissues, and high CAT expression was correlated with a favorable survival prognosis in LIHC. The expression of the CAT gene was associated with an inhibition of the “cell cycle” pathway. HepG2 and Hep3B cells’ growth was increased with a decrease in CAT expression by silencing its mRNA. As silencing of CAT in HepG2 and Hep3B cells, and its association with an increase in the expression of PLK1, CCNB1, CDC20, and PTTG1. A comparative 426 drug response in LIHC cells with different CAT expression, SU11274, a Met inhibitor, could serve as a therapeutic option when CAT levels are low in LIHC cells. Conclusions Our findings revealed that Met inhibitors could potentially control tumor progression and be used as a therapeutic option against LIHC with low CAT.

Funder

Show Chwan Memorial Hospital

Kaohsiung Veterans General Hospital

Veterans Affairs Council

Publisher

Walter de Gruyter GmbH

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