Cuproptosis-related lncRNAs forecast the prognosis of acute myeloid leukemia.
Acute myeloid leukemia (AML) is a highly heterogeneous cluster of hematologic malignancies. Leukemic stem cells (LSCs) are one of the culprits for the persistence and relapse of AML. The discovery of copper-induced cell death, namely cuproptosis, gives bright insights into the treatment of AML. Analogous to copper ions, long non-coding RNAs (lncRNAs) are not bystanders for AML progression, especially for LSC physiology. Uncovering the involvement of cuproptosis-related lncRNAs in AML will benefit clinical management.
Detection of prognostic relevant cuproptosis-related lncRNAs are carried out by Pearson correlation analysis and univariate Cox analysis with RNA sequencing data of The Cancer Genome Atlas-Acute Myeloid Leukemia (TCGA-LAML) cohort. After the least absolute shrinkage and selection operator (LASSO) regression and the subsequent multivariate Cox analysis, a cuproptosis-related risk score (CuRS) system was derived to weigh the risk of AML patients. Thereafter, AML patients were classified into two groups by their risk property which was validated with principal component analysis (PCA), risk curves, Kaplan-Meier survival analysis, the combined receiver operating characteristic (ROC) curves, and nomogram. Variations in biological pathways and divergences in immune infiltration and immune-related processes between groups were resolved by GSEA and CIBERSORT algorism, respectively. Response to chemotherapies were scrutinized as well. The expression profiles of the candidate lncRNAs were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and the specific mechanisms of lncRNA FAM30A were determined by transcriptomic analysis.
We fabricated an efficient prognostic signature named CuRS incorporating 4 lncRNAs (TRAF3IP2-AS1, NBR2, TP53TG1, and FAM30A) relevant to immune environment and chemotherapy responsiveness. The relevance of lncRNA FAM30A with proliferation, migration ability, Daunorubicin resistance and its reciprocal action with AUF1 were demonstrated in an LSC cell line. Transcriptomic analysis suggested correlations between FAM30A and T cell differentiation and signaling, intercellular junction genes.
The prognostic signature CuRS can guide prognostic stratification and personalized AML therapy. Analysis of FAM30A offers a foundation for investigating LSC-targeted therapies.
Zhang T
，Liao D
，Hu Y
《-》
A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for acute myeloid leukemia.
Cuproptosis 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).
RNA-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.
Five 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.
A cuproptosis-related lncRNA signature was established to predict the prognosis and inform on potential therapeutic strategies for AML patients.
Li P
，Li J
，Wen F
，Cao Y
，Luo Z
，Zuo J
，Wu F
，Li Z
，Li W
，Wang F
... -
《Frontiers in Oncology》
Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia.
Long non-coding RNAs (lncRNAs) have been reported to have a crucial impact on the pathogenesis of acute myeloid leukemia (AML). Cuproptosis, a copper-triggered modality of mitochondrial cell death, might serve as a promising therapeutic target for cancer treatment and clinical outcome prediction. Nevertheless, the role of cuproptosis-related lncRNAs in AML is not fully understood.
The RNA sequencing data and demographic characteristics of AML patients were downloaded from The Cancer Genome Atlas database. Pearson correlation analysis, the least absolute shrinkage and selection operator algorithm, and univariable and multivariable Cox regression analyses were applied to identify the cuproptosis-related lncRNA signature and determine its feasibility for AML prognosis prediction. The performance of the proposed signature was evaluated via Kaplan-Meier survival analysis, receiver operating characteristic curves, and principal component analysis. Functional analysis was implemented to uncover the potential prognostic mechanisms. Additionally, quantitative real-time PCR (qRT-PCR) was employed to validate the expression of the prognostic lncRNAs in AML samples.
A signature consisting of seven cuproptosis-related lncRNAs (namely NFE4, LINC00989, LINC02062, AC006460.2, AL353796.1, PSMB8-AS1, and AC000120.1) was proposed. Multivariable cox regression analysis revealed that the proposed signature was an independent prognostic factor for AML. Notably, the nomogram based on this signature showed excellent accuracy in predicting the 1-, 3-, and 5-year survival (area under curve = 0.846, 0.801, and 0.895, respectively). Functional analysis results suggested the existence of a significant association between the prognostic signature and immune-related pathways. The expression pattern of the lncRNAs was validated in AML samples.
Collectively, we constructed a prediction model based on seven cuproptosis-related lncRNAs for AML prognosis. The obtained risk score may reveal the immunotherapy response in patients with this disease.
Zhu Y
，He J
，Li Z
，Yang W
... -
《BMC BIOINFORMATICS》
Establishment of a prognostic signature for lung adenocarcinoma using cuproptosis-related lncRNAs.
To establish a prognostic signature for lung adenocarcinoma (LUAD) based on cuproptosis-related long non-coding RNAs (lncRNAs), and to study the immune-related functions of LUAD.
First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate COX analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate COX analysis were performed to analyze the cuproptosis-related lncRNAs, and a prognostic signature was established. Second, univariate COX analysis and multivariate COX analysis were performed for independent prognostic analyses. Receiver operating characteristic (ROC) curves, C index, survival curve, nomogram, and principal component analysis (PCA) were performed to evaluate the results of the independent prognostic analyses. Finally, gene enrichment analyses and immune-related function analyses were also carried out.
(1) A total of 1,297 cuproptosis-related lncRNAs were screened. (2) A LUAD prognostic signature containing 13 cuproptosis-related lncRNAs was constructed (NIFK-AS1, AC026355.2, SEPSECS-AS1, AL360270.1, AC010999.2, ABCA9-AS1, AC032011.1, AL162632.3, LINC02518, LINC0059, AL031600.2, AP000346.1, AC012409.4). (3) The area under the multi-indicator ROC curves at 1, 3, and 5 years were AUC1 = 0.742, AUC2 = 0.708, and AUC3 = 0.762, respectively. The risk score of the prognostic signature could be used as an independent prognostic factor that was independent of other clinical indicators. (4) The results of gene enrichment analyses showed that 13 biomarkers were primarily related to amoebiasis, the wnt signaling pathway, hematopoietic cell lineage. The ssGSEA volcano map showed significant differences between high- and low-risk groups in immune-related functions, such as human leukocyte antigen (HLA), Type_II_IFN_Reponse, MHC_class_I, and Parainflammation (P < 0.001).
Thirteen cuproptosis-related lncRNAs may be clinical molecular biomarkers for the prognosis of LUAD.
Yalimaimaiti S
，Liang X
，Zhao H
，Dou H
，Liu W
，Yang Y
，Ning L
... -
《BMC BIOINFORMATICS》
ResearchGate
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