Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma

Author:

Lee Ji Ah1,Choi Hei-Gwon2,Eun Hyuk Soo234ORCID,Bu Jiyoon15,Jang Tae Min5,Lee Jeongdong6,Son Chae Yeon5,Kim Min Seok6,Rou Woo Sun37ORCID,Kim Seok Hyun34,Lee Byung Seok34,Kim Ha Neul2,Lee Tae Hee6ORCID,Jeon Hong Jae37

Affiliation:

1. Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea

2. Department of Medical Science, Chungnam National University, 266, Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea

3. Department of Internal Medicine, College of Medicine, Chungnam National University, 266, Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea

4. Department of Internal Medicine, Chungnam National University Hospital, 282, Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea

5. Department of Biological Engineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea

6. Department of Biomedical Laboratory Science, Daegu Health College, 15 Yeongsong-ro, Buk-gu, Daegu 41453, Republic of Korea

7. Department of Internal Medicine, Chungnam National University Sejong Hospital, 20, Bodeum 7-ro, Sejong 30099, Republic of Korea

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Funder

Ministry of Science and Technology

Korea Technology & Information Promotion Agency for SMEs

National Research Council of Science & Technology

Ministry of Health & Welfare

Gangwon Techno Park

Inha University

Chungnam National University Hospital Research Fund

Leaders in Industry-university Cooperation 3.0 Project

Korean Government

Daegu Technopark

Chungnam National University Research Grant

Ministry of Science and ICT

Publisher

MDPI AG

Reference35 articles.

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5. Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B;Aghoram;Cochrane Database Syst. Rev.,2012

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