A Novel Defined Pyroptosis-Related Gene Signature for the Prognosis of Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Datasets
2.2. Differential Analysis of Pyroptosis-Related Genes
2.3. Consensus Clustering Analysis
2.4. Prognostic Signature Construction
2.5. Independent Prognostic Analysis
2.6. Construction and Evaluation of a Nomogram
2.7. Drug Sensitivity Evaluation
2.8. Functional Enrichment and Immune Microenvironment Analysis
2.9. Statistical Analysis
3. Results
3.1. Identification of Differentially Expressed Pyroptosis Genes between Normal and AML Samples
3.2. AML Clustering Based on the DEGs
3.3. Construction of a Prognostic Model in the AML Cohort
3.4. External Validation of the Prognostic Model
3.5. Evaluation of the Independent Prognostic Value of the Risk Model
3.6. Establishment and Evaluation of a Nomogram Model
3.7. Difference of Immune Microenvironment between Subgroups
3.8. Drug Response Analysis of High and Low-Risk Patients to Chemotherapy
3.9. Functional Enrichment Analyses of the Risk Model
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Bullinger, L.; Döhner, K.; Döhner, H. Genomics of Acute Myeloid Leukemia Diagnosis and Pathways. J. Clin. Oncol. 2017, 35, 934–946. [Google Scholar] [CrossRef] [PubMed]
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Creutzig, U.; Kutny, M.A.; Barr, R.; Schlenk, R.F.; Ribeiro, R.C. Acute myelogenous leukemia in adolescents and young adults. Pediatr. Blood Cancer 2018, 65, e27089. [Google Scholar] [CrossRef] [PubMed]
- Juliusson, G.; Antunovic, P.; Derolf, A.; Lehmann, S.; Möllgård, L.; Stockelberg, D.; Tidefelt, U.; Wahlin, A.; Höglund, M. Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 2009, 113, 4179–4187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oran, B.; Weisdorf, D.J. Survival for older patients with acute myeloid leukemia: A population-based study. Haematologica 2012, 97, 1916–1924. [Google Scholar] [CrossRef]
- Appelbaum, F.R.; Gundacker, H.; Head, D.R.; Slovak, M.L.; Willman, C.L.; Godwin, J.E.; Anderson, J.E.; Petersdorf, S.H. Age and acute myeloid leukemia. Blood 2006, 107, 3481–3485. [Google Scholar] [CrossRef] [Green Version]
- Papaemmanuil, E.; Gerstung, M.; Bullinger, L.; Gaidzik, V.I.; Paschka, P.; Roberts, N.D.; Potter, N.E.; Heuser, M.; Thol, F.; Bolli, N.; et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N. Engl. J. Med. 2016, 374, 2209–2221. [Google Scholar] [CrossRef]
- Sasaki, K.; Ravandi, F.; Kadia, T.M.; DiNardo, C.D.; Short, N.J.; Borthakur, G.; Jabbour, E.; Kantarjian, H.M. De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer 2021, 127, 2049–2061. [Google Scholar] [CrossRef]
- Döhner, H.; Wei, A.H.; Appelbaum, F.R.; Craddock, C.; DiNardo, C.D.; Dombret, H.; Ebert, B.L.; Fenaux, P.; Godley, L.A.; Hasserjian, R.P.; et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022, 140, 1345–1377. [Google Scholar] [CrossRef]
- Eisfeld, A.K. Unbiased decision-making for acute myeloid leukemia still needed. Haematologica 2022. [Google Scholar] [CrossRef]
- Shi, J.; Gao, W.; Shao, F. Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem. Sci. 2017, 42, 245–254. [Google Scholar] [CrossRef]
- Yu, P.; Zhang, X.; Liu, N.; Tang, L.; Peng, C.; Chen, X. Pyroptosis: Mechanisms and diseases. Signal Transduct. Target. Ther. 2021, 6, 128. [Google Scholar] [CrossRef]
- Xia, X.; Wang, X.; Cheng, Z.; Qin, W.; Lei, L.; Jiang, J.; Hu, J. The role of pyroptosis in cancer: Pro-cancer or pro-“host”? Cell Death Dis. 2019, 10, 650. [Google Scholar] [CrossRef] [Green Version]
- Liu, X.; Zhang, Z.; Ruan, J.; Pan, Y.; Magupalli, V.G.; Wu, H.; Lieberman, J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 2016, 535, 153–158. [Google Scholar] [CrossRef] [Green Version]
- Downs, K.P.; Nguyen, H.; Dorfleutner, A.; Stehlik, C. An overview of the non-canonical inflammasome. Mol. Asp. Med. 2020, 76, 100924. [Google Scholar] [CrossRef]
- Fang, Y.; Tian, S.; Pan, Y.; Li, W.; Wang, Q.; Tang, Y.; Yu, T.; Wu, X.; Shi, Y.; Ma, P.; et al. Pyroptosis: A new frontier in cancer. Biomed. Pharmacother. 2020, 121, 109595. [Google Scholar] [CrossRef]
- Hergueta-Redondo, M.; Sarrió, D.; Molina-Crespo, Á.; Megias, D.; Mota, A.; Rojo-Sebastian, A.; García-Sanz, P.; Morales, S.; Abril, S.; Cano, A.; et al. Gasdermin-B promotes invasion and metastasis in breast cancer cells. PLoS ONE 2014, 9, e90099. [Google Scholar] [CrossRef] [Green Version]
- Gao, J.; Qiu, X.; Xi, G.; Liu, H.; Zhang, F.; Lv, T.; Song, Y. Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non-small cell lung cancer. Oncol. Rep. 2018, 40, 1971–1984. [Google Scholar] [CrossRef] [Green Version]
- Man, S.M.; Karki, R.; Kanneganti, T.D. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol. Rev. 2017, 277, 61–75. [Google Scholar] [CrossRef] [Green Version]
- Frank, D.; Vince, J.E. Pyroptosis versus necroptosis: Similarities, differences, and crosstalk. Cell Death Differ. 2019, 26, 99–114. [Google Scholar] [CrossRef]
- Wilkerson, M.D.; Hayes, D.N. ConsensusClusterPlus: A class discovery tool with confidence assessments and item tracking. Bioinformatics 2010, 26, 1572–1573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Geeleher, P.; Cox, N.; Huang, R.S. pRRophetic: An R package for prediction of clinical chemotherapeutic response from tumor gene expression levels. PLoS ONE 2014, 9, e107468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, F.-F.; Liu, C.-J.; Liu, L.-L.; Zhang, Q.; Guo, A.-Y. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief. Bioinform. 2020, 22, bbaa176. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Qin, X.; Liang, J.; Ge, P. Induction of Pyroptosis: A Promising Strategy for Cancer Treatment. Front. Oncol. 2021, 11, 635774. [Google Scholar] [CrossRef] [PubMed]
- Wu, D.; Wei, C.; Li, Y.; Yang, X.; Zhou, S. Pyroptosis, a New Breakthrough in Cancer Treatment. Front. Oncol. 2021, 11, 698811. [Google Scholar] [CrossRef]
- Van Opdenbosch, N.; Lamkanfi, M. Caspases in Cell Death, Inflammation, and Disease. Immunity 2019, 50, 1352–1364. [Google Scholar] [CrossRef]
- Lacey, C.A.; Mitchell, W.J.; Dadelahi, A.S.; Skyberg, J.A. Caspase-1 and Caspase-11 Mediate Pyroptosis, Inflammation, and Control of Brucella Joint Infection. Infect. Immun. 2018, 86, e00361-18. [Google Scholar] [CrossRef] [Green Version]
- Liu, J.; Kang, R.; Tang, D. ESCRT-III-mediated membrane repair in cell death and tumor resistance. Cancer Gene Ther. 2021, 28, 1–4. [Google Scholar] [CrossRef]
- McCullough, J.; Frost, A.; Sundquist, W.I. Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes. Annu. Rev. Cell Dev. Biol. 2018, 34, 85–109. [Google Scholar] [CrossRef]
- Wu, P.; Shi, J.; Sun, W.; Zhang, H. Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer. Cancer Cell Int. 2021, 21, 523. [Google Scholar] [CrossRef]
- Zhang, M.; Cheng, Y.; Xue, Z.; Sun, Q.; Zhang, J. A novel pyroptosis-related gene signature predicts the prognosis of glioma through immune infiltration. BMC Cancer 2021, 21, 1311. [Google Scholar] [CrossRef]
- Ye, Y.; Dai, Q.; Qi, H. A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer. Cell Death Discov. 2021, 7, 71. [Google Scholar] [CrossRef]
- Binder, S.; Luciano, M.; Horejs-Hoeck, J. The cytokine network in acute myeloid leukemia (AML): A focus on pro- and anti-inflammatory mediators. Cytokine Growth Factor Rev. 2018, 43, 8–15. [Google Scholar] [CrossRef]
- Ustun, C.; Miller, J.S.; Munn, D.H.; Weisdorf, D.J.; Blazar, B.R. Regulatory T cells in acute myelogenous leukemia: Is it time for immunomodulation? Blood 2011, 118, 5084–5095. [Google Scholar] [CrossRef] [Green Version]
- Shenghui, Z.; Yixiang, H.; Jianbo, W.; Kang, Y.; Laixi, B.; Yan, Z.; Xi, X. Elevated frequencies of CD4⁺ CD25⁺ CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int. J. Cancer 2011, 129, 1373–1381. [Google Scholar] [CrossRef]
- Ersvaer, E.; Liseth, K.; Skavland, J.; Gjertsen, B.T.; Bruserud, Ø. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol. 2010, 11, 38. [Google Scholar] [CrossRef] [Green Version]
- Curti, A.; Pandolfi, S.; Valzasina, B.; Aluigi, M.; Isidori, A.; Ferri, E.; Salvestrini, V.; Bonanno, G.; Rutella, S.; Durelli, I.; et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25− into CD25+ T regulatory cells. Blood 2006, 109, 2871–2877. [Google Scholar] [CrossRef]
- Cools, N.; Van Tendeloo, V.F.; Smits, E.L.; Lenjou, M.; Nijs, G.; Van Bockstaele, D.R.; Berneman, Z.N.; Ponsaerts, P. Immunosuppression induced by immature dendritic cells is mediated by TGF-β/IL-10 double-positive CD4+ regulatory T cells. J. Cell. Mol. Med. 2008, 12, 690–700. [Google Scholar] [CrossRef] [Green Version]
- McGranahan, N.; Furness, A.J.S.; Rosenthal, R.; Ramskov, S.; Lyngaa, R.; Saini, S.K.; Jamal-Hanjani, M.; Wilson, G.A.; Birkbak, N.J.; Hiley, C.T.; et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016, 351, 1463–1469. [Google Scholar] [CrossRef] [Green Version]
- Dijkgraaf, G.J.P.; Alicke, B.; Weinmann, L.; Januario, T.; West, K.; Modrusan, Z.; Burdick, D.; Goldsmith, R.; Robarge, K.; Sutherlin, D.; et al. Small Molecule Inhibition of GDC-0449 Refractory Smoothened Mutants and Downstream Mechanisms of Drug Resistance. Cancer Res. 2011, 71, 435–444. [Google Scholar] [CrossRef]
- Bensi, L.; Longo, R.; Vecchi, A.; Messora, C.; Garagnani, L.; Bernardi, S.; Tamassia, M.G.; Sacchi, S. Bcl-2 oncoprotein expression in acute myeloid leukemia. Haematologica 1995, 80, 98–102. [Google Scholar] [PubMed]
- Bertram, K.; Leary, P.J.; Boudesco, C.; Fullin, J.; Stirm, K.; Dalal, V.; Zenz, T.; Tzankov, A.; Müller, A. Inhibitors of Bcl-2 and Bruton’s tyrosine kinase synergize to abrogate diffuse large B-cell lymphoma growth in vitro and in orthotopic xenotransplantation models. Leukemia 2022, 36, 1035–1047. [Google Scholar] [CrossRef] [PubMed]
- Löwenberg, B.; Pabst, T.; Vellenga, E.; van Putten, W.; Schouten, H.C.; Graux, C.; Ferrant, A.; Sonneveld, P.; Biemond, B.J.; Gratwohl, A.; et al. Cytarabine Dose for Acute Myeloid Leukemia. N. Engl. J. Med. 2011, 364, 1027–1036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandez, H.F.; Sun, Z.; Yao, X.; Litzow, M.R.; Luger, S.M.; Paietta, E.M.; Racevskis, J.; Dewald, G.W.; Ketterling, R.P.; Bennett, J.M.; et al. Anthracycline Dose Intensification in Acute Myeloid Leukemia. N. Engl. J. Med. 2009, 361, 1249–1259. [Google Scholar] [CrossRef] [Green Version]
- Zhou, J.; Ching, Y.Q.; Chng, W.-J. Aberrant nuclear factor-kappa B activity in acute myeloid leukemia: From molecular pathogenesis to therapeutic target. Oncotarget 2015, 6, 5490–5500. [Google Scholar] [CrossRef] [Green Version]
- Braun, T.; Carvalho, G.; Fabre, C.; Grosjean, J.; Fenaux, P.; Kroemer, G. Targeting NF-κB in hematologic malignancies. Cell Death Differ. 2006, 13, 748–758. [Google Scholar] [CrossRef] [Green Version]
- Schnerch, D.; Yalcintepe, J.; Schmidts, A.; Becker, H.; Follo, M.; Engelhardt, M.; Wasch, R. Cell cycle control in acute myeloid leukemia. Am. J. Cancer Res. 2012, 2, 508–528. [Google Scholar]
- Récher, C. Clinical Implications of Inflammation in Acute Myeloid Leukemia. Front. Oncol. 2021, 11, 623952. [Google Scholar] [CrossRef]
- Wang, F. A Novel Defined Pyroptosis-Related Gene Signature for Predicting Prognosis of Acute Myeloid Leukemia. Res. Sq. 2022, 1–21. [Google Scholar] [CrossRef]
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Huang, K.; Xie, L.; Wang, F. A Novel Defined Pyroptosis-Related Gene Signature for the Prognosis of Acute Myeloid Leukemia. Genes 2022, 13, 2281. https://doi.org/10.3390/genes13122281
Huang K, Xie L, Wang F. A Novel Defined Pyroptosis-Related Gene Signature for the Prognosis of Acute Myeloid Leukemia. Genes. 2022; 13(12):2281. https://doi.org/10.3390/genes13122281
Chicago/Turabian StyleHuang, Kecheng, Linka Xie, and Fan Wang. 2022. "A Novel Defined Pyroptosis-Related Gene Signature for the Prognosis of Acute Myeloid Leukemia" Genes 13, no. 12: 2281. https://doi.org/10.3390/genes13122281
APA StyleHuang, K., Xie, L., & Wang, F. (2022). A Novel Defined Pyroptosis-Related Gene Signature for the Prognosis of Acute Myeloid Leukemia. Genes, 13(12), 2281. https://doi.org/10.3390/genes13122281