Page 57 - GPD-2-1

Gene & Protein in Disease Pyroptosis-related LncRNAs in pediatric AML

rate of 20–40% and a relapse rate of 30% . Although there (TME), which is a dynamic network that includes tumor
[1]
have been improvements in the prognosis of pediatric cells, immune cells, and stromal cells . We hypothesize
[15]
AML patients as a result of the latest advances in areas that PR-lncRNAs may affect progression of pediatric AML
such as molecular pathological diagnostic techniques, risk and the prognosis of these patients by interacting with the
stratification, and targeted supportive care, the overall immune microenvironment. In this study, based on the
survival (OS) in 2021 remains below 70% [1-3] . As known Therapeutically Applicable Research to Generate Effective
to all, its clinical outcomes and genetic backgrounds are Treatment (TARGET) database, the relationship between
different in each age group . To date, there are only a PR-lncRNAs and the prognosis of pediatric AML patients
[4]
number of well-designed and systematic studies that focus was investigated; an evaluation of the predictive ability of
on the molecular mechanisms of pediatric AML. More the prognostic signature constructed by seven significant
efforts are thus needed to identify potential biomarkers PR-lncRNAs was performed; and an exploration of
that can monitor the prognosis of pediatric AML patients, whether PR-lncRNAs have an impact on the molecular
as well as provide more efficient therapeutic strategies. microenvironment in pediatric AML was also carried out.

Pyroptosis is a gasdermin-mediated programmed cell 2. Materials and methods
death (PCD) initiated by inflammasomes that are critical
for immunity [5-7] . The previous research has found that 2.1. Data acquisition
pyroptosis causes the release of inflammatory mediators The gene expression and clinical data of 1474 pediatric
IL-1β and IL-18 and prolongs the exposure of cells to an AML samples were retrieved from the TARGET database
inflammatory environment, which may add to the risk of up to March 1, 2022 (https://ocg.cancer.gov/programs/
tumorigenesis . To date, many studies have reported that target). After excluding samples with incomplete clinical
[8]
pyroptosis is crucial in tumor invasion, proliferation, and data, replications, and normal samples, 1300 pediatric
metastasis, and it can regulate AML progression . Existing AML samples were included for subsequent analyses.
[7]
studies have found that dipeptidyl peptidase (DPP)8 and
DPP9 (DPP8/9), which are tiny molecules inhibiting 2.2. Identification of pyroptosis-related lncRNAs and
serine dipeptidases, are related to pyrolysis through their consensus clustering analyses
activation of pro-caspase-1 in human AML cell lines and The lncRNA annotation file from the GENCODE website
primary AML samples, which, in turn, trigger cell lysis (GRCh38) (https://www.gencodegenes.org/human/) was
and death, known as pyroptosis, and inhibit human AML used to distinguish lncRNAs and protein-coding genes.
progression. This is thought to be a promising therapeutic Meanwhile, 52 PR-lncRNAs were obtained from a website
strategy for AML . Besides, due to the physical interaction (http://www.broad.mit.edu/gsea/msigdb/) and relevant
[9]
between caspase-associated recruitment domain 8 studies, as shown in Table S1. Pearson product-moment
(CARD8) and caspase-1, the production of caspase-1- correlation coefficient was employed to distinguish
dependent interleukin (IL)-1β is negatively regulated in PR-lncRNAs with |Pearson R| > 0.4 and P < 0.001. Univariate
THP-1 (a human-monocyte cell line derived from an AML Cox regression analysis (Uni-Cox) was implemented
patient); this is similar to TP92 [10,11] . Taking these results to screen prognosis and pyroptosis-related lncRNAs
together, the role pyroptosis plays in pediatric AML which (PPR-lncRNAs), while taking overall survival (OS) as the
cannot be overlooked. endpoint. The pediatric AML samples were divided into
Long non-coding RNAs (lncRNAs) are expressed different clusters according to PPR-lncRNAs expressions
transcripts that do not encode proteins that are more by R package “ConsensusClusterPlus.”
than 200 nt in length. They are involved in the onset and
development of AML [12,13] . Besides, it has been found that 2.3. Relationship and differences among different
lncRNAs play crucial roles in humorous cellular processes, clusters
including pyroptosis. LncRNAs can regulate the expression The difference in OS among the clusters was determined
of proteins related to the pyroptosis signaling pathway using Kaplan–Meier (K-M) curves and a log-rank test.
indirectly through miRNAs . This kind of modulation Kyoto Encyclopedia of Genes and Genomes (KEGG)
[14]
exists in the pathological process of tumorigenesis as gene sets in Gene Set Enrichment Analysis (GSEA)
well. However, there is little research on pyroptosis- (version 4.2.3) were applied to three clusters to explore
related lncRNAs (PR-lncRNAs) in pediatric AML. In the distinctions of enriched pathways. The Estimation
addition, PR-lncRNAs’ role in the prognosis of pediatric of STromal and Immune cells in MAlignant Tumor
AML patients and its biological mechanism remain tissues using Expression data (ESTIMATE) scoring of the
unclear. Furthermore, current evidence has suggested a tumor microenvironment and the relative proportions
link between pyroptosis and tumor microenvironment of 22 immune cell infiltrations were calculated using

Volume 2 Issue 1 (2023) 2 https://doi.org/10.36922/gpd.v2i1.230