Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma

Tang, Haijia; Hu, Xiaoxin; Xu, Fujiang; Lin, Kefei; Xu, Wenhao; Huang, Haineng; Zhang, Hailiang; Xiao, Yu; Sun, Dongdong; Liu, Wangrui; Wei, Shiyin

doi:10.7150/jca.64765



International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

Global reach, higher impact

Full Text | PDF

J Cancer 2022; 13(9):2740-2750. doi:10.7150/jca.64765 This issue Cite

Research Paper

Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma

Haijia Tang^1*, Xiaoxin Hu^2*, Fujiang Xu^3*, Kefei Lin^4*, Wenhao Xu³, Haineng Huang⁵, Hailiang Zhang³, Yu Xiao^5✉, Dongdong Sun^6✉, Wangrui Liu^5,7✉, Shiyin Wei^5✉

1. Department of Integrated Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
2. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
3. Department of Urology, Fudan University Shanghai Cancer Center, School of Life Sciences, Fudan University, Shanghai, China
4. Department of Urology, PKUCare CNOOC Hospital,Tianjin,300452, China
5. Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China
6. School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
7. Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
*Equal contribution

✉ Corresponding authors: Dongdong Sun (Email: sunddedu.cn), School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Yu Xiao (Email:yjxiaoyucom), Affiliated Hospital of Youjiang Medi More

Citation:

Tang H, Hu X, Xu F, Lin K, Xu W, Huang H, Zhang H, Xiao Y, Sun D, Liu W, Wei S. Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma. J Cancer 2022; 13(9):2740-2750. doi:10.7150/jca.64765. https://www.jcancer.org/v13p2740.htm

Other styles

Abstract

Backgrounds: Liver hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and POLE, playing an important role in maintaining genetic stability, is closely connected with cancer prognosis. This study aimed to explore the significance role of POLE in HCC prognosis, clinical treatment and tumor immune microenvironment based on large-scale multiply cohorts.

Methods: First, we found that the expression of POLE was prominently higher in tumor tissues than in normal tissues, and was closely related to clinical stage, grade and patient outcomes. Second, we found that patients with high POLE expression had significantly aggressive progression, indicating effective predictive role of POLE expression for Asian, male, low-risk HCC patients. Additionally, POLE mutation frequency was detected in several datasets with available genomic-wide data.

Results: 130 HCC samples from real-world Renji cohort were included to demonstrate that elevated POLE expression was significantly connected to the invasive progression and poor prognosis. More importantly, the expression of POLE was closely related to the anti-tumoral activity of immune cells and immune checkpoints expression, suggesting a bright prospect of POLE as a predictive biomarker in immunotherapy.

Conclusion: In conclusion, this study revealed that high expression of POLE significantly correlated to the malignant progression, poor prognosis and anti-tumoral activity of immune cells in HCC. Thus, POLE could function as a biomarker for the early diagnosis, prognosis, immune-excluded tumor microenvironment and response to immunotherapy of HCC.

Keywords: POLE, liver hepatocellular carcinoma, tumor immune microenvironment, prognosis

Citation styles

APA

Tang, H., Hu, X., Xu, F., Lin, K., Xu, W., Huang, H., Zhang, H., Xiao, Y., Sun, D., Liu, W., Wei, S. (2022). Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma. Journal of Cancer, 13(9), 2740-2750. https://doi.org/10.7150/jca.64765.

ACS

Tang, H.; Hu, X.; Xu, F.; Lin, K.; Xu, W.; Huang, H.; Zhang, H.; Xiao, Y.; Sun, D.; Liu, W.; Wei, S. Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma. J. Cancer 2022, 13 (9), 2740-2750. DOI: 10.7150/jca.64765.

NLM

CSE

Tang H, Hu X, Xu F, Lin K, Xu W, Huang H, Zhang H, Xiao Y, Sun D, Liu W, Wei S. 2022. Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma. J Cancer. 13(9):2740-2750.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.