PMID- 37304546
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230613
IS  - 2219-6803 (Electronic)
IS  - 2218-676X (Print)
IS  - 2218-676X (Linking)
VI  - 12
IP  - 5
DP  - 2023 May 31
TI  - Cuproptosis-related lncRNAs forecast the prognosis of acute myeloid leukemia.
PG  - 1175-1195
LID - 10.21037/tcr-22-2526 [doi]
AB  - BACKGROUND: 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. METHODS: 
      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. RESULTS: 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. CONCLUSIONS: The prognostic signature CuRS can 
      guide prognostic stratification and personalized AML therapy. Analysis of FAM30A 
      offers a foundation for investigating LSC-targeted therapies.
CI  - 2023 Translational Cancer Research. All rights reserved.
FAU - Zhang, Tong
AU  - Zhang T
AD  - Department of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Liao, Danying
AU  - Liao D
AD  - Department of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Hu, Yu
AU  - Hu Y
AD  - Department of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20230418
PL  - China
TA  - Transl Cancer Res
JT  - Translational cancer research
JID - 101585958
PMC - PMC10248575
OTO - NOTNLM
OT  - AUF1
OT  - Acute myeloid leukemia (AML)
OT  - FAM30A
OT  - cuproptosis
OT  - long non-coding RNAs (lncRNAs)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://tcr.amegroups.com/article/view/10.21037/tcr-22-2526/coif). The authors 
      report that this research was funded by the National Natural Science Foundation 
      of China (No. 82000141 to DL and No. 31620103909 to YH). The authors have no 
      other conflicts of interest to declare.
EDAT- 2023/06/12 06:42
MHDA- 2023/06/12 06:43
PMCR- 2023/05/31
CRDT- 2023/06/12 04:10
PHST- 2022/11/01 00:00 [received]
PHST- 2023/03/30 00:00 [accepted]
PHST- 2023/06/12 06:43 [medline]
PHST- 2023/06/12 06:42 [pubmed]
PHST- 2023/06/12 04:10 [entrez]
PHST- 2023/05/31 00:00 [pmc-release]
AID - tcr-12-05-1175 [pii]
AID - 10.21037/tcr-22-2526 [doi]
PST - ppublish
SO  - Transl Cancer Res. 2023 May 31;12(5):1175-1195. doi: 10.21037/tcr-22-2526. Epub 
      2023 Apr 18.