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Background. Liver hepatocellular carcinoma (LIHC) is the most frequently seen type of primary liver cancer. Cuproptosis is a novel form of cell death highly associated with mitochondrial metabolism. However, the clinical impact and pertinent mechanism of cuproptosis genes in LIHC remain largely unknown. Methods. From public databases, we systematically assessed common genes from LIHC differentially expressed genes (DEGs) and cuproptosis-related genes using bioinformatics analysis. These common genes were then analyzed by enrichment analysis, mutation analysis, risk score model, and others to find candidate hub genes related to LIHC and cuproptosis. Next, hub genes were determined by expression, clinical factors, immunoassay, and prognostic nomogram. Results. Based on 129 cuproptosis-related genes and 3492 LIHC DEGs, we totally identified 21 downregulated and 18 upregulated common genes, and they were enriched in pathways, such as zinc ion homeostasis and oxidative phosphorylation. In the mutation analysis, missense mutation was the most common type in LIHC patients, and the common gene F5 had the highest mutation frequency. After LASSO-Cox regression analysis and prognostic analysis, CDK1, ABCB6, LCAT, and COA6 were identified as prognostic signature genes. Among them, ABCB6 and LCAT were lowly expressed in tumors, and CDK1 and COA6 were highly expressed in tumors. In addition, ABCB6 and LCAT were negatively correlated with 6 kinds of immune cells, while CDK1 and COA6 were positively correlated with them. CDK1 and COA6 were identified as hub genes related to LIHC by Cox regression analysis and prognostic nomogram. Conclusion. CDK1 and COA6 are two oncogenes in LIHC, which are involved in the molecular mechanism of cuproptosis and LIHC. Besides, CDK1 and COA6 can positively regulate the expressions of immune cells in LIHC. In clinical practice, they can be used as immunotherapeutic targets and prognostic predictors in LIHC, which sheds new light on the scientific fields of cuproptosis and LIHC. [ABSTRACT FROM AUTHOR]

Objective. Growing evidence shows that enhancer RNAs (eRNAs) are pivotal for tumor progression. In this research, our team aimed to identify the survival-related eRNAs and further explore their potential function in glioblastoma (GBM). Methods. RNA-sequencing data in 31 tumor types were acquired from TCGA datasets. The survival-related eRNAs were identified by the use of Kaplan-Meier survival analyses and Spearman's correlation analyses. KEGG pathway enrichment analysis was completed to investigate the underlying signal paths of the critical eRNA. Pancancer assays were applied to explore the association between CYP1B1-AS1 and CYP1B1. Results. We identified 74 survival-related eRNAs and focused on CYP1B1-AS1 which displayed the greatest cor value. CYP1B1 was identified as a regulatory target of CYP1B1-AS1. KEGG analyses suggested that CYP1B1-AS1 might play an essential role through CK-CKR mutual effect, complement and coagulation cascades, TNF signal path, and JAK-STAT signal path. The pancancer verification outcomes revealed that CYP1B1-AS1 was related to survival in 4 cancers, i.e., LIHC, KIRP, KICH, and KIRC. Association was discovered between CYP1B1-AS1 and the targeted gene, CYP1B1, in 29 cancer types. Conclusion. The outcomes herein provided the first evidence that overexpression of CYP1B1-AS1 might be a potential molecular biomarker for predicting the prognosis of patients with GBM. [ABSTRACT FROM AUTHOR]

Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma (UC). To evaluate the predictive and prognostic value of PD-L1 on response and survival in UC patients after cystectomy, chemotherapy, or anti-PD-1/PD-L1 therapy, a systematic review of PubMed, Embase, Web of Science, and the Cochrane Library was performed. A total of 2154 patients from 14 published studies were included. In all UC patients after cystectomy, tumour cell (TC) PD-L1 expression was not associated with the OS or PFS. For the subset of patients with organ-confined disease, TC PD-L1 expression significantly predicted OS after cystectomy (P = 0.0004). There was no significant evidence of an association between TC PD-L1 status and ORR or OS for UC patients treated with platinum-based chemotherapy. For UC patients treated with anti-PD-1/PD-L1 therapy, TC PD-L1 expression ≥ 5 % could predict the response (P = 0.005), but not for the 1% cut-off (P ≥ 0.05). As for PD-L1 expression in tumour-inflating immune cells (TIICs), both subsets with IC2/3 vs. IC0/1 and IC1/2/3 vs. IC0 were associated with ORR to anti-PD-1/PD-L1 therapy. In the TIIC subset, IC2/3 vs. IC0/1 of PD-L1 was associated with higher CR (P = 0.002), PR (P = 0.04), and PD (P = 0.007). Further, higher TIIC PD-L1 status benefited from longer PFS (P < 0.001), but was not associated with OS in UC patients with anti-PD-1/PD-L1 therapy. Our study suggested that TIIC PD-L1 expression with 5% cut-off was valuable as a predictive and prognostic biomarker for ORR and PFS in UC patients with anti-PD-1/PD-L1 therapy. [ABSTRACT FROM AUTHOR]