Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is usually associated with poor prognosis and low complete remission (CR) rate due to individual biological heterogeneity. Pyroptosis is a special form of inflammatory programmed cell death related to the progression, treatment response, and prognosis of multiple tumors....
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.898236/full |
| _version_ | 1818545571222257664 |
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| author | Jingjing Pan Yinyan Jiang Changhong Li Ting Jin Kang Yu Zhenlin Jin |
| author_facet | Jingjing Pan Yinyan Jiang Changhong Li Ting Jin Kang Yu Zhenlin Jin |
| author_sort | Jingjing Pan |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) is usually associated with poor prognosis and low complete remission (CR) rate due to individual biological heterogeneity. Pyroptosis is a special form of inflammatory programmed cell death related to the progression, treatment response, and prognosis of multiple tumors. However, the potential connection of pyroptosis-related genes (PRGs) and AML still remains unclear. We described the genetic and transcriptional alterations of PRGs in 151 AML samples and presented a consensus clustering of these patients into two subtypes with distinct immunological and prognostic characteristics. Cluster A, associated with better prognosis, was characterized by relatively lower PRG expression, activated immune cells, higher immune scores in the tumor microenvironment (TME), and downregulation of immunotherapy checkpoints. Subsequently, a PRG score was constructed to predict overall survival (OS) of AML patients by using univariate and multivariate Cox regression analysis, and its immunological characteristics and predictive capability were further validated by 1,054 AML samples in external datasets. Besides an immune-activated status, low-PRG score cohorts exhibited higher chemotherapeutic drug sensitivity and significant positive correlation with the cancer stem cell (CSC) index. Combined with age, clinical French-American-British (FAB) subtypes, and PRG score, we successfully constructed a nomogram to effectively predict the 1-/3-/5-year survival rate of AML patients, and the predictive capability was further validated in multiple external datasets with a high area under the curve (AUC) value. The various transcriptomic analysis helps us screen significant pyroptosis-related signatures of AML and provide a new clinical application of PRG scores in predicting the prognosis and benefits of treatment for AML patients. |
| first_indexed | 2024-12-12T07:41:52Z |
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| id | doaj.art-128ac3216a5943da86f26c78cfffdc41 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T07:41:52Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-128ac3216a5943da86f26c78cfffdc412022-12-22T00:32:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.898236898236Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid LeukemiaJingjing Pan0Yinyan Jiang1Changhong Li2Ting Jin3Kang Yu4Zhenlin Jin5Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Operating Room, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaAcute myeloid leukemia (AML) is usually associated with poor prognosis and low complete remission (CR) rate due to individual biological heterogeneity. Pyroptosis is a special form of inflammatory programmed cell death related to the progression, treatment response, and prognosis of multiple tumors. However, the potential connection of pyroptosis-related genes (PRGs) and AML still remains unclear. We described the genetic and transcriptional alterations of PRGs in 151 AML samples and presented a consensus clustering of these patients into two subtypes with distinct immunological and prognostic characteristics. Cluster A, associated with better prognosis, was characterized by relatively lower PRG expression, activated immune cells, higher immune scores in the tumor microenvironment (TME), and downregulation of immunotherapy checkpoints. Subsequently, a PRG score was constructed to predict overall survival (OS) of AML patients by using univariate and multivariate Cox regression analysis, and its immunological characteristics and predictive capability were further validated by 1,054 AML samples in external datasets. Besides an immune-activated status, low-PRG score cohorts exhibited higher chemotherapeutic drug sensitivity and significant positive correlation with the cancer stem cell (CSC) index. Combined with age, clinical French-American-British (FAB) subtypes, and PRG score, we successfully constructed a nomogram to effectively predict the 1-/3-/5-year survival rate of AML patients, and the predictive capability was further validated in multiple external datasets with a high area under the curve (AUC) value. The various transcriptomic analysis helps us screen significant pyroptosis-related signatures of AML and provide a new clinical application of PRG scores in predicting the prognosis and benefits of treatment for AML patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.898236/fullacute myeloid leukemiapyroptosismolecular subtypetumor microenvironmentprognosistherapeutic sensitivity |
| spellingShingle | Jingjing Pan Yinyan Jiang Changhong Li Ting Jin Kang Yu Zhenlin Jin Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia Frontiers in Oncology acute myeloid leukemia pyroptosis molecular subtype tumor microenvironment prognosis therapeutic sensitivity |
| title | Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia |
| title_full | Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia |
| title_fullStr | Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia |
| title_full_unstemmed | Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia |
| title_short | Characteristics of Pyroptosis-Related Subtypes and Novel Scoring Tool for the Prognosis and Chemotherapy Response in Acute Myeloid Leukemia |
| title_sort | characteristics of pyroptosis related subtypes and novel scoring tool for the prognosis and chemotherapy response in acute myeloid leukemia |
| topic | acute myeloid leukemia pyroptosis molecular subtype tumor microenvironment prognosis therapeutic sensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.898236/full |
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