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Tumor Discovery Pyroptosis-related genes in breast cancer progression

Table 2. The pathway of 15 genes (null: The pathway has not been fully elucidated in breast cancer)
Name Related cancer Pathway
High-risk genes
FIBCD1 Breast cancer, gastric cancer, etc. Inhibit inflammatory mediators and mucinous proteins
(GeneCards)
CACNA1H Breast cancer, prostate cancer, etc. β-catenin/HMGA2 signaling 13
HSPB8 Breast cancer, lung cancer, gastric cancer, etc. Pass the G0/G1 phase restriction point 26
PXDNL Breast cancer Null 29,36,37
Low-risk genes
PSME2 Breast cancer, gastric cancer, etc. Activate proteasomes to generate the antigenic peptides
presented by major histocompatibility complex class I
molecules 38
DIRAS3 Breast cancer, ovarian cancer, pancreatic cancer, Inhibit signaling through PI3 kinase/AKT, JAK/STAT, and
etc. RAS/MAPK 16
RAC2 Breast cancer, pancreatic cancer, etc. Activated by the combination Gαi-2 and ELMO1/Dock180
comple× 17
MMP7 Breast cancer, gastric cancer, prostate cancer, colon Suppress the recruitment of CD4+/CD8+TILs or the
cancer, etc. expression of CXCL16 18
MATK Breast cancer, colon cancer, etc. Inhibit the activation of Src family kinases 22
RGS1 Breast cancer, ovarian cancer, gastric cancer, etc. Suppress CXCR4 39
KLHDC7B Breast cancer, bladder cancer, etc. STAT1-mediated interferon signaling pathway 40
DEF6 Breast cancer, ovarian cancer, colon cancer, etc. Suppress E-cadherin expression and the regulation of
epithelial-mesenchymal transition transcription factors 20
ARMH1/APOBEC3D/APOBEC3F Acute myeloid leukemia, breast cancer, etc. Null 41
Abbreviations: CXCL16: C-X-C motif chemokine ligand 16; TILs: Tumor-infiltrating lymphocytes; FIBCD1: Fibrinogen C domain-containing 1;
CACNA1H: Calcium voltage-gated channel subunit alpha1 H; HSPB8: Heat shock protein family B (small) member 8; PXDNL: Peroxidasin-like;
PSME2: Proteasome activator subunit 2; ARMH1: Armadillo-like helical domain-containing 1; DIRAS3: DIRAS family GTPase 3; MMP7: Matrix
metallopeptidase 7; MATK: Megakaryocyte-associated tyrosine kinase; RGS1: Regulator of G protein signaling 1.

studied in BC literature. Thus, these four genes can be As shown in Table 2, we performed qPCR and
used as target genes for further BC research. In addition, western blotting to investigate the expression level
we found that CACNA1H, RAC2, DIRAS3, and DEF6 are of pyroptosis-related genes in BC based on gene and
intimately associated with the invasion and metastasis of protein levels. As shown in Figure 10, the qPCR results
BC cells, so new ways might be found to prevent and treat are generally consistent with those of Western blotting.
BC or improve its prognosis by promoting the combined In MDA-MB-231 cells and MDA-MB-468 cells, the
up-regulation or down-regulation of these four genes. In expressions of APOBEC3D and APOBEC3F were much
addition, the down-regulation of DEF6 is closely related to higher than in BT549 and MCF7. It is worth noting that
MMPs, suggesting that these two genes might be potential the proteins APOBEC3D and APOBEC3F were used
indicators for further prognosis of BC. with the same antibody in western blotting. Moreover,

The innovation of this study lies in the construction of a low expression of APOBEC3D in MCF7 was also
42
a highly reliable prognosis model based on 15 risk genes. reported by Chen et al. In addition, the expressions
We identified specific links between different genes, of PXDNL and ARMH1 were significantly higher in BC
which promoted multidisciplinary analysis and provided cells, indicating that they may be used as therapeutic
43,44
personalized prevention and treatment for different targets in BC.
patients with BC. However, the limitation of this study Similarly, there are several limitations to this study.
is that the P-value of the prognosis model is 0.01, and Primarily, it relies on bioinformatics analysis using data
the genes selected are large, which is not conducive to from public databases, meaning that all predictions require
analysis. Reducing the P-value could potentially narrow further experimental validation. While we conducted
45
down the number of prognostic genes and refine the some preliminary verification, such as in vitro verification
model. of gene expression and protein levels in BC cell lines,

Volume 3 Issue 3 (2024) 13 doi: 10.36922/td.3469