Background: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLCA) remains poorly described. Methods:We downloaded the transcriptome sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and lasso Cox regression analyses were performed to construct the prognostic risk signature, the predictive accuracy of which was validated in the subsequent independence and stratification analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the underlying molecular mechanisms involved in the signature to explore therapeutic vulnerabilities and potential targets in BLCA. Tumor mutational burden (TMB) and tumor immune dysfunction and exclusion (TIDE) were used to estimate the response to immune checkpoint inhibitors (ICIs). We further explored the potential new drug-target candidates based on the half maximal inhibitory concentration for this patient population.Results: Fifteen cuproptosis-related lncRNAs significantly associated with survival were identified to construct the risk signature based on the normalized expression level and regression coefficient of each gene.The patients with BLCA and high-risk scores defined by the signature were associated with worse survival outcomes. The differentially expressed genes (DEGs) between the 2 risk groups had different biological activity. Furthermore, the patients in the low-risk group exhibited a higher TMB index and a lower TIDE score. The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score.Conclusions: Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population.
Background: Liver hepatocellular carcinoma (LIHC), whose incidence is increasing globally, is one of the most prevalent malignant cancers. RAS-related pathways are involved in the cell proliferation, migration, apoptosis, and metabolism in LIHC. Long noncoding RNAs (lncRNAs) also play important roles in the progression and prognosis of LIHC. However, the clinical role, prognostic significance, and immune regulation of RAS-related lncRNAs in LIHC remains unclear. Our study aims to construct and validate a RAS-related lncRNA prognostic risk signature that can estimate the prognosis and response to immunotherapy in LIHC. Methods:The clinical information and corresponding messenger RNA (mRNA)/lncRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and 502 RAS-related lncRNAs were identified by Pearson correlation analysis. A prognostic risk signature with 5 RAS-related lncRNAs was then developed based on the Cox regression and least absolute shrinkage and selection operator (LASSO) algorithm analyses. Subsequently, Kaplan-Meier survival curve, receiver operating characteristic (ROC) curve, and the nomogram were established to evaluate the predictive accuracy of the signature. In addition, the immune microenvironment, tumor mutation burden, and drug sensitivity associated with the signature were also analyzed in LIHC.Results: Compared with the low-risk groups, the high-risk groups had an unfavorable outcome.Multivariate regression analysis revealed that the risk score signature was the independent prognostic factor superior to the other clinical variables. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses demonstrated that the risk score was highly associated with the nuclear division, DNA replication, and immune response. The group with high risk tended to hold a lower immune escape rate and better immunotherapy efficacy, while the group with low risk was more sensitive to some small molecular targeted drugs. Conclusions:We developed a RAS-related lncRNA risk signature that was highly associated with the prognosis and response to immunotherapy and targeted drugs and which provided novel mechanistic insights into the personalized treatment and potential drug selection for patients with LIHC.
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