A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for acute myeloid leukemia

Abstract

BackgroundCuproptosis is a type of programmed cell death that is involved in multiple physiological and pathological processes, including cancer. We constructed a prognostic cuproptosis-related long non-coding RNA (lncRNA) signature for acute myeloid leukemia (AML).MethodsRNA-seq and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) database. The cuproptosis-related prognostic lncRNAs were identified by co-expression and univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) was performed to construct a cuproptosis-related lncRNA signature, after which the AML patients were classified into two risk groups based on the risk model. Kaplan-Meier, ROC, univariate and multivariate Cox regression, nomogram, and calibration curves analyses were used to evaluate the prognostic value of the model. Then, expression levels of the lncRNAs in the signature were investigated in AML samples by quantitative polymerase chain reaction (qPCR). KEGG functional analysis, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. The sensitivities for potential therapeutic drugs for AML were also investigated.ResultsFive hundred and three lncRNAs related to 19 CRGs in AML samples from the TCGA database were obtained, and 21 differentially expressed lncRNAs were identified based on the 2-year overall survival (OS) outcomes of AML patients. A 4-cuproptosis-related lncRNA signature for survival was constructed by LASSO Cox regression. High-risk AML patients exhibited worse outcomes. Univariate and multivariate Cox regression analyses demonstrated the independent prognostic value of the model. ROC, nomogram, and calibration curves analyses revealed the predictive power of the signature. KEGG pathway and ssGSEA analyses showed that the high-risk group had higher immune activities. Lastly, AML patients from different risk groups showed differential responses to various agents.ConclusionA cuproptosis-related lncRNA signature was established to predict the prognosis and inform on potential therapeutic strategies for AML patients.

Cuproptosis-Related lncRNA Gene Signature Establishes a Prognostic Model of Gastric Adenocarcinoma and Evaluate the Effect of Antineoplastic Drugs

“…Peter Tsvetkov et al [ 7 ] recently described a novel type of cell death called cuproptosis, which is distinct from the known processes of death such apoptosis, pyroptosis, necrosis, and ferroptosis. Cuproptosis has been shown to be associated with the occurrence and development of a variety of cancers, including liver cancer [ 8 ], colorectal cancer [ 9 ], esophageal cancer [ 10 ], and some hematologic malignancies, including the acute myeloid leukemia [ 11 ]. These studies suggest that cuproptosis may be associated with a wider range of malignancies.…”

Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia

“…The construction of the prognosis prediction model might It should be noted that the use of cuproptosis-related lncRNAs for prognostic prediction has been reported in various cancers, including osteosarcoma [34], colon cancer [25], gastric cancer [35], hepatocellular carcinoma [23], and head and neck squamous carcinoma [36]. A recent study identified four cuproptosis-related lncR-NAs involved in the prediction of the 2-year OS outcomes in AML patients [13]. In the present study, seven cuproptosis-related lncRNAs were utilized in the construction of a prognostic model for 1-, 3-, and 5-year AML prognosis prediction, which showed good prediction performance (all AUC > 0.8).…”

“…For example, cuproptosis was used to predict clinical outcomes and immune response in bladder cancer [9], breast cancer [10], colorectal cancer [11], and prostate cancer [12]. A more recent study suggested that cuproptosis-related genes might be critically involved in the 2-year AML prognosis and the immune response to treatment [13]. However, the role of cuproptosis in the pathogenesis and the long-term prognosis of AML has not yet been fully elucidated.…”

Long non‐coding RNAs regulate treatment outcome in leukemia: What have we learnt recently?

“…Although multiple prognostic factors including leukemia type, age, white blood cell count, cytogenetics, and recurrent mutations have been identified, the outcome prediction and risk stratification in leukemia patients are still not optimal and need improvement. Given lncRNAs' important role in regulating leukemia patient outcome, there are studies to investigate the potential of incorporating lncRNAs to improve the current prediction model for drug resistance and exploiting them as potential targets to overcome therapeutic resistance 98,99 . Indeed, the lncRNA landscape has been characterized in multiple leukemia types and corresponding lncRNA scores have been developed for outcome prediction.…”