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

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.

Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway

“…Based on The Cancer Genome Atlas (TCGA) datasets and 961 ubiquitin-proteasome system genes (UPSGs), Liu et al [ 11 ] found that DDB1 and CUL4 associated factor 13 ( DCAF13 ), cell division cycle 20 ( CDC20 ), and proteasome 20S subunit beta 5 ( PSMB5 ) have excellent performance to predict the survival of liver cancer patients. Zhang et al [ 12 ] identified a seven-UPSG prognostic signature, of which autophagy related 10 ( ATG10 ) was found to participate in liver cancer development and prognosis through autophagy, immune response, and tumor metastasis. Therefore, proteasome inhibitors, as a class of potential and effective anti-tumor drugs, have attracted a growing body of attention from researchers.…”