Liver Regeneration-Related Genes of Nontumor Liver Tissues Predict the Prognosis of Patients with Hepatocellular Carcinoma

Yanchao Xu; Yunzheng Li; Yanjun Lu; Weihong Wang; Zhaowu Lian; Zijie Wu; Binghua Li; Decai Yu

doi:10.2147/JHC.S433688

Liver Regeneration-Related Genes of Nontumor Liver Tissues Predict the Prognosis of Patients with Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2023 Dec 7:10:2197-2209. doi: 10.2147/JHC.S433688. eCollection 2023.

Authors

Yanchao Xu^#¹, Yunzheng Li^#², Yanjun Lu^#³, Weihong Wang¹, Zhaowu Lian³, Zijie Wu⁴, Binghua Li¹, Decai Yu^{1

2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People's Republic of China.
² State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People's Republic of China.
³ Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
⁴ Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients is influenced by various factors, including surgical methods and energy metabolism. This study aims to provide a prognostic model based on genes related to liver regeneration that can predict the prognosis of non-tumor tissues in HCC patients.

Patients and methods: A total of 584 non-tumor tissues from HCC patients were collected from three independent databases. Kaplan-Meier survival curves were used to identify prognostic liver-regeneration genes. Subsequently, a prognostic indicator, designated as the Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts were used to verify the relationship between LR score and prognosis in non-tumor tissues of HCC patients. Furthermore, a liver regeneration-related model was established to validate key genes identified through LASSO Cox regression analysis.

Results: We constructed a gene set comprising 24 liver regeneration-related genes, and the LR score was utilized to predict the prognosis of HCC patients based on its levels in non-tumor tissues. In non-tumor tissues of HCC patients, higher LR scores were associated with improved prognosis. Higher LR scores in non-tumor tissues indicate improved liver metabolism in HCC patients, revealed by Enrichment analysis. LASSO Cox regression analysis identified two key genes, DHTKD1 (dehydrogenase E1 and transketolase domain containing 1) and PHYH (phytanoyl-CoA 2-hydroxylase), and higher expression levels of these genes in non-tumor tissues were correlated with better prognosis. The expression levels of these two genes also changed corresponding to the progression of liver regeneration.

Conclusion: In summary, our study has introduced a novel LR gene signature for HCC patients, providing a predictive model for estimating clinical prognosis from non-tumor tissues. The LR score demonstrates promise as a reliable indicator for predicting overall survival in HCC.

Keywords: HCC; hepatocellular carcinoma; liver regeneration; non-tumor tissue; prognosis.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82002509, 82173129), the Special Fund of Nanjing Health Science and Technology Development (No. YKK21079), the Start-up Funding for Talent Introduction of Drum Tower Hospital (RC2023-032), the China Postdoctoral Science Foundation (no. 2023M731622) and the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-MS-12).