System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma

Ke-Jie He; Zhiqiang Nie

doi:10.3389/fonc.2023.1221498

System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma

Front Oncol. 2023 Sep 13:13:1221498. doi: 10.3389/fonc.2023.1221498. eCollection 2023.

Authors

Ke-Jie He¹, Zhiqiang Nie²

Affiliations

¹ The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
² Global Health Research Center, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.

Abstract

Background: Liver cancer is a leading cause of cancer-related deaths worldwide. Lysosomal dysfunction is implicated in cancer progression; however, prognostic prediction models based on lysosome-related genes (LRGs) are lacking in liver cancer. This study aimed to establish an LRG-based model to improve prognosis prediction and explore potential therapeutic targets in liver cancer.

Methods: Expression profiles of 61 LRGs were analyzed in The Cancer Genome Atlas liver cancer cohorts. There were 14 LRGs identified, and their association with clinical outcomes was evaluated. Unsupervised clustering, Cox regression, and functional assays were performed.

Results: Patients were classified into high-risk and low-risk subgroups based on the 14 LRGs. The high-risk group had significantly worse overall survival. Aberrant immune infiltration and checkpoint expression were observed in the high-risk group. Furthermore, HPS4 was identified as an independent prognostic indicator. Knockdown of HPS4 suppressed liver cancer cell proliferation and induced apoptosis.

Conclusion: This study developed an LRG-based prognostic model to improve risk stratification in liver cancer. The potential value of HPS4 as a therapeutic target and biomarker was demonstrated. Regulation of HPS4 may offer novel strategies for precision treatment in liver cancer patients.

Keywords: HPS4; LIHC; chemotherapy response; copy number variation; gene mutation; immune; methylation; prognostic signature.

Grants and funding

This project was funded by Quzhou Municipal Science and Technology Bureau (2023K117) and Quzhou Medical and Health personnel scientific research fund project (KYQD2022-18).