Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

Jianxiang Zhang; Liwen Liu; Zenghan Wang; Mingyang Hou; Zihui Dong; Jia Yu; Ranran Sun; Guangying Cui

doi:10.3389/fphar.2023.1172908

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

Front Pharmacol. 2023 Apr 25:14:1172908. doi: 10.3389/fphar.2023.1172908. eCollection 2023.

Authors

Jianxiang Zhang¹, Liwen Liu², Zenghan Wang², Mingyang Hou³, Zihui Dong², Jia Yu², Ranran Sun², Guangying Cui²

Affiliations

¹ Department of General Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: Ubiquitin-proteasome system (UPS) is implicated in cancer occurrence and progression. Targeting UPS is emerging as a promising therapeutic target for cancer treatment. Nevertheless, the clinical significance of UPS in hepatocellular carcinoma (HCC) has not been entirely elucidated. Methods: Differentially expressed UPS genes (DEUPS) were screened from LIHC-TCGA datasets. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analysis were conducted to establish a UPS-based prognostic risk model. The robustness of the risk model was further validated in HCCDB18, GSE14520, and GSE76427 cohorts. Subsequently, immune features, clinicopathologic characteristics, enrichment pathways, and anti-tumor drug sensitivity of the model were further evaluated. Moreover, a nomogram was established to improve the predictive ability of the risk model. Results: Seven UPS-based signatures (ATG10, FBXL7, IPP, MEX3A, SOCS2, TRIM54, and PSMD9) were developed for the prognostic risk model. Individuals with HCC with high-risk scores presented a more dismal prognosis than those with low-risk scores. Moreover, larger tumor size, advanced TNM stage, and tumor grade were observed in the high-risk group. Additionally, cell cycle, ubiquitin-mediated proteolysis, and DNA repair pathways were intimately linked to the risk score. In addition, obvious immune cell infiltration and sensitive drug response were identified in low-risk patients. Furthermore, both nomogram and risk score showed a significant prognosis-predictive ability. Conclusion: Overall, we established a novel UPS-based prognostic risk model in HCC. Our results will facilitate a deep understanding of the functional role of UPS-based signature in HCC and provide a reliable prediction of clinical outcomes and anti-tumor drug responses for patients with HCC.

Keywords: drug sensitivity; hepatocellular carcinoma; prognosis; risk model; ubiquitin-proteasome system.

Grants and funding

Funding from the Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (Grant Nos ZYCXTD2023002 and QNCXTD2023002).