Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram
BackgroundInterleukin-9 (IL9) plays a critical role in immunity and the pathogenesis of endometrial cancer (EC), especially endometrioid EC (EEC). This study aimed to identify the IL9+ immune cell subsets and their pleiotropic functions and establish an optimized prognostic nomogram towards the prom...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.544248/full |
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| author | Huan Tong Hao Feng Hao Feng Xiang Hu Meng-fei Wang Yun-feng Song Xiao-li Wen Yi-ran Li Xiao-ping Wan Xiao-ping Wan |
| author_facet | Huan Tong Hao Feng Hao Feng Xiang Hu Meng-fei Wang Yun-feng Song Xiao-li Wen Yi-ran Li Xiao-ping Wan Xiao-ping Wan |
| author_sort | Huan Tong |
| collection | DOAJ |
| description | BackgroundInterleukin-9 (IL9) plays a critical role in immunity and the pathogenesis of endometrial cancer (EC), especially endometrioid EC (EEC). This study aimed to identify the IL9+ immune cell subsets and their pleiotropic functions and establish an optimized prognostic nomogram towards the promotion of personalized treatment of EEC.Methods1,417 EC patients were involved in the present study. 143 patients from the tertiary gynecology centers in Shanghai between 2013 and 2019 were recruited, and the study protocol was approved by the Institutional Review Board (IRB) of Shanghai First Maternity and Infant Hospital. The genomic data of the other 1,274 patients were extracted from the TCGA and the MSKCC datasets, respectively. Immune and stromal scores were calculated using the ESTIMATE R tool, and the tumor infiltration of immune cells was analyzed using the TIMER platform. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism and R studio.Results552 genes that were correlated with leukocyte infiltration, lymphocyte activation, and regulation of innate immune response were up-regulated in the high immune score group. More IL9+ cell infiltration was detected in the highly and moderately differentiated EC (p = 0.04). High IL9+ lymphocyte infiltration was related to a better overall survival (p = 0.0027). IL9 positive cell clusters included ILC2s, Vδ2 γδT cells, mast cells, macrophages, and Th9 cells. Parameters such as FIGO stage, IL9 score, Vδ2 + γδT cell infiltration, classification of differentiation, and diabetes mellitus were assigned a weighted number of points in the nomogram for a specific predicted 3-, 5- and 10-year overall survival (OS). IL9–IL9R axis played a vital role in EEC, IL9R positive cell subgroups were also identified, and the related function was analyzed in the present study. Additionally, PR (Progesterone Receptor, or PGR) expression was relevant to a higher density of IL9+ lymphocyte infiltration. However, PGRMC1 (Progesterone Receptor Membrane Component 1) was negatively relevant to IL9R (p = 4.26e-8).ConclusionWe observed a significant infiltration of IL9+ cells and the overrepresentation of IL-9R in tissue specimens of patients in EC cases. The nomogram incorporating the IL9 could accurately predict individualized survival probability in EEC. Additionally, this study not only established a prognostic nomogram but also assist in the firmer understanding of the relevance of the IL9-IL9R axis and IL9-producing cells in EC immunity. |
| first_indexed | 2024-12-23T04:38:10Z |
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| id | doaj.art-c76bfadc43a847d8813de556f3895fcf |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-23T04:38:10Z |
| publishDate | 2020-11-01 |
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| spelling | doaj.art-c76bfadc43a847d8813de556f3895fcf2022-12-21T17:59:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.544248544248Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic NomogramHuan Tong0Hao Feng1Hao Feng2Xiang Hu3Meng-fei Wang4Yun-feng Song5Xiao-li Wen6Yi-ran Li7Xiao-ping Wan8Xiao-ping Wan9Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaUniversity Hospital of Munich, Ludwig-Maximilians-University of Munich, Munich, GermanyClinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaClinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaClinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaClinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaClinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaBackgroundInterleukin-9 (IL9) plays a critical role in immunity and the pathogenesis of endometrial cancer (EC), especially endometrioid EC (EEC). This study aimed to identify the IL9+ immune cell subsets and their pleiotropic functions and establish an optimized prognostic nomogram towards the promotion of personalized treatment of EEC.Methods1,417 EC patients were involved in the present study. 143 patients from the tertiary gynecology centers in Shanghai between 2013 and 2019 were recruited, and the study protocol was approved by the Institutional Review Board (IRB) of Shanghai First Maternity and Infant Hospital. The genomic data of the other 1,274 patients were extracted from the TCGA and the MSKCC datasets, respectively. Immune and stromal scores were calculated using the ESTIMATE R tool, and the tumor infiltration of immune cells was analyzed using the TIMER platform. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism and R studio.Results552 genes that were correlated with leukocyte infiltration, lymphocyte activation, and regulation of innate immune response were up-regulated in the high immune score group. More IL9+ cell infiltration was detected in the highly and moderately differentiated EC (p = 0.04). High IL9+ lymphocyte infiltration was related to a better overall survival (p = 0.0027). IL9 positive cell clusters included ILC2s, Vδ2 γδT cells, mast cells, macrophages, and Th9 cells. Parameters such as FIGO stage, IL9 score, Vδ2 + γδT cell infiltration, classification of differentiation, and diabetes mellitus were assigned a weighted number of points in the nomogram for a specific predicted 3-, 5- and 10-year overall survival (OS). IL9–IL9R axis played a vital role in EEC, IL9R positive cell subgroups were also identified, and the related function was analyzed in the present study. Additionally, PR (Progesterone Receptor, or PGR) expression was relevant to a higher density of IL9+ lymphocyte infiltration. However, PGRMC1 (Progesterone Receptor Membrane Component 1) was negatively relevant to IL9R (p = 4.26e-8).ConclusionWe observed a significant infiltration of IL9+ cells and the overrepresentation of IL-9R in tissue specimens of patients in EC cases. The nomogram incorporating the IL9 could accurately predict individualized survival probability in EEC. Additionally, this study not only established a prognostic nomogram but also assist in the firmer understanding of the relevance of the IL9-IL9R axis and IL9-producing cells in EC immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2020.544248/fullendometrial carcinomaγδT cellsinterleukin-9nomogramsurvival analysis |
| spellingShingle | Huan Tong Hao Feng Hao Feng Xiang Hu Meng-fei Wang Yun-feng Song Xiao-li Wen Yi-ran Li Xiao-ping Wan Xiao-ping Wan Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram Frontiers in Immunology endometrial carcinoma γδT cells interleukin-9 nomogram survival analysis |
| title | Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram |
| title_full | Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram |
| title_fullStr | Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram |
| title_full_unstemmed | Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram |
| title_short | Identification of Interleukin-9 Producing Immune Cells in Endometrial Carcinoma and Establishment of a Prognostic Nomogram |
| title_sort | identification of interleukin 9 producing immune cells in endometrial carcinoma and establishment of a prognostic nomogram |
| topic | endometrial carcinoma γδT cells interleukin-9 nomogram survival analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.544248/full |
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