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. 2022 Nov 25:12:1043862.
doi: 10.3389/fonc.2022.1043862. eCollection 2022.

Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma

Lu-Shan Peng  1 , Sai-Li Duan  2 , Run-Qi Li  3 , Dan Wang  1 , Ying-Ying Han  1 , Tao Huang  1 , Yu-Pei Yu  1 , Chun-Lin Ou  1   4 , Jun-Pu Wang  1   3   5
Affiliations

Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma

Lu-Shan Peng et al. Front Oncol. .

Abstract

Background: The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood.

Methods: In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape.

Results: The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers.

Conclusions: GSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

Keywords: GSDM family; biomarker; immune infiltration; lung adenocarcinoma; methylation; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Differential expression of GSDMs between tumor and adjacent normal tissues. The expression of (A) GSDMA, (B) GSDMB, (C) GSDMC, (D) GSDMD, (E) GSDME, and (F) PJVK in different tumors and normal tissues based on the Timer database. * means p<0.05, ** means p<0.005, and *** means p<0.001.
Figure 2
Figure 2
Expression of six GSDM family members in LUAD. (A) The UALCAN database was used to retrieve the GSDMs’ mRNA expression profiles. (B) The THPA database was used to collect IHC images of GSDM family members from LUAD tissues and normal lung tissues, representing the GSDM protein expression levels. (C) The IHC result of GSDMD expression in LAUD and adjacent normal lung tissue. *** means p<0.001.
Figure 3
Figure 3
GSDMs family member-associated clinical pathology characteristics of patients with LUAD. (A) The associations between GSDM transcript levels and individual cancer stages of LUAD. (B) The expression of GSDM family members in different LUAD histological subtypes. (C) The GEPIA database was used to analyze the relationships between GSDM transcript levels and OS of LUAD patients. * means p<0.05, ** means p<0.005, and *** means p<0.001.
Figure 4
Figure 4
Genetic alterations and methylation levels of GSDM family members in LUAD. (A) The cBioPortal database was used to achieve the genetic alteration profiles of GSDMs. (B) The DiseaseMeth database was used to evaluate the DNA methylation levels of GSDM family members in LUAD.
Figure 5
Figure 5
PPI network and the biological pathways of GSDM family members. (A) STRING and Cytoscape were used to build the PPI network. The WebGestalt database was used for the GSDM-related co-expressed molecules to analyze the GO functional enrichment analysis (B) and the KEGG pathway analysis (C).
Figure 6
Figure 6
Correlation between immune cell infiltration and GSDM mRNA expression levels. The TIMER database was used to evaluate the association of GSDMA (A), GSDMB (B), GSDMC (C), GSDMD (D), GSDME (E), and PJVK (F) expression and immune cell infiltration. The ssGSEA method from R package GSVA was used to evaluate the association of six GSDM family members and NK cell (G).
Figure 7
Figure 7
Correlation between GSDMs and immune check-points related genes in LUAD. We used the STRING database to analyze the correlation between GSDMA (A), GSDMB (B), and GSDMD (C) and immune related genes.
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References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Bray, global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2021) 71:209–49. doi: 10.3322/caac.21660 - DOI - PubMed
    1. Tomášková H, Horáček J, Šlachtová H, Šplíchalová A, Riedlová P, Dalecká A, et al. . Analysis of histopathological findings of lung carcinoma in Czech black coal miners in association with coal workers' pneumoconiosis. Int J Environ Res Public Health (2022) 19(2):710. doi: 10.3390/ijerph19020710 - DOI - PMC - PubMed
    1. Wang Y, Nie H, He X, Liao Z, Zhou Y, Zhou J, et al. . The emerging role of super enhancer-derived noncoding RNAs in human cancer. Theranostics (2020) 10:11049–62. doi: 10.7150/thno.49168 - DOI - PMC - PubMed
    1. Sarrió D, Martínez-Val J, Molina-Crespo Á., Sánchez L, Moreno-Bueno G. The multifaceted roles of gasdermins in cancer biology and oncologic therapies. Biochim Biophys Acta Rev Cancer (2021) 1876:188635. doi: 10.1016/j.bbcan.2021.188635 - DOI - PubMed
    1. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. . Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ (2018) 25:486–541. doi: 10.1038/s41418-017-0012-4 - DOI - PMC - PubMed

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