Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients
BackgroundIncreasing evidence indicates that immune cell infiltration (ICI) affects the prognosis of multiple cancers. This study aims to explore the immunotypes and ICI-related biomarkers in ovarian cancer.MethodsThe ICI levels were quantified with the CIBERSORT and ESTIMATE algorithms. The unsuper...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.916251/full |
| _version_ | 1811290945812955136 |
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| author | Na Zhao Yujuan Xing Yanfang Hu Hao Chang |
| author_facet | Na Zhao Yujuan Xing Yanfang Hu Hao Chang |
| author_sort | Na Zhao |
| collection | DOAJ |
| description | BackgroundIncreasing evidence indicates that immune cell infiltration (ICI) affects the prognosis of multiple cancers. This study aims to explore the immunotypes and ICI-related biomarkers in ovarian cancer.MethodsThe ICI levels were quantified with the CIBERSORT and ESTIMATE algorithms. The unsupervised consensus clustering method determined immunotypes based on the ICI profiles. Characteristic genes were identified with the Boruta algorithm. Then, the ICI score, a novel prognostic marker, was generated with the principal component analysis of the characteristic genes. The relationships between the ICI scores and clinical features were revealed. Further, an ICI signature was integrated after the univariate Cox, lasso, and stepwise regression analyses. The accuracy and robustness of the model were tested by three independent cohorts. The roles of the model in the immunophenoscores (IPS), tumor immune dysfunction and exclusion (TIDE) scores, and immunotherapy responses were also explored. Finally, risk genes (GBP1P1, TGFBI, PLA2G2D) and immune cell marker genes (CD11B, NOS2, CD206, CD8A) were tested by qRT-PCR in clinical tissues.ResultsThree immunotypes were identified, and ICI scores were generated based on the 75 characteristic genes. CD8 TCR pathways, chemokine-related pathways, and lymphocyte activation were critical to immunophenotyping. Higher ICI scores contributed to better prognoses. An independent prognostic factor, a three-gene signature, was integrated to calculate patients’ risk scores. Higher TIDE scores, lower ICI scores, lower IPS, lower immunotherapy responses, and worse prognoses were revealed in high-risk patients. Macrophage polarization and CD8 T cell infiltration were indicated to play potentially important roles in the development of ovarian cancer in the clinical validation cohort.ConclusionsOur study characterized the immunotyping landscape and provided novel immune infiltration-related prognostic markers in ovarian cancer. |
| first_indexed | 2024-04-13T04:21:05Z |
| format | Article |
| id | doaj.art-32d2eb9120cc4579bf4424f77ec8250a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T04:21:05Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-32d2eb9120cc4579bf4424f77ec8250a2022-12-22T03:02:43ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.916251916251Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer PatientsNa Zhao0Yujuan Xing1Yanfang Hu2Hao Chang3Department of Gynecology, Dongying People’s Hospital, Dongying, ChinaDepartment of Gynecology, Dongying People’s Hospital, Dongying, ChinaDepartment of Gynecology, Dongying People’s Hospital, Dongying, ChinaDepartment of Cancer Research, Hanyu Biomed Center Beijing, Beijing, ChinaBackgroundIncreasing evidence indicates that immune cell infiltration (ICI) affects the prognosis of multiple cancers. This study aims to explore the immunotypes and ICI-related biomarkers in ovarian cancer.MethodsThe ICI levels were quantified with the CIBERSORT and ESTIMATE algorithms. The unsupervised consensus clustering method determined immunotypes based on the ICI profiles. Characteristic genes were identified with the Boruta algorithm. Then, the ICI score, a novel prognostic marker, was generated with the principal component analysis of the characteristic genes. The relationships between the ICI scores and clinical features were revealed. Further, an ICI signature was integrated after the univariate Cox, lasso, and stepwise regression analyses. The accuracy and robustness of the model were tested by three independent cohorts. The roles of the model in the immunophenoscores (IPS), tumor immune dysfunction and exclusion (TIDE) scores, and immunotherapy responses were also explored. Finally, risk genes (GBP1P1, TGFBI, PLA2G2D) and immune cell marker genes (CD11B, NOS2, CD206, CD8A) were tested by qRT-PCR in clinical tissues.ResultsThree immunotypes were identified, and ICI scores were generated based on the 75 characteristic genes. CD8 TCR pathways, chemokine-related pathways, and lymphocyte activation were critical to immunophenotyping. Higher ICI scores contributed to better prognoses. An independent prognostic factor, a three-gene signature, was integrated to calculate patients’ risk scores. Higher TIDE scores, lower ICI scores, lower IPS, lower immunotherapy responses, and worse prognoses were revealed in high-risk patients. Macrophage polarization and CD8 T cell infiltration were indicated to play potentially important roles in the development of ovarian cancer in the clinical validation cohort.ConclusionsOur study characterized the immunotyping landscape and provided novel immune infiltration-related prognostic markers in ovarian cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.916251/fullimmunophenotypingimmune checkpointsprognosisovarian cancerimmune cell infiltrationimmunotherapy |
| spellingShingle | Na Zhao Yujuan Xing Yanfang Hu Hao Chang Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients Frontiers in Oncology immunophenotyping immune checkpoints prognosis ovarian cancer immune cell infiltration immunotherapy |
| title | Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients |
| title_full | Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients |
| title_fullStr | Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients |
| title_full_unstemmed | Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients |
| title_short | Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients |
| title_sort | exploration of the immunotyping landscape and immune infiltration related prognostic markers in ovarian cancer patients |
| topic | immunophenotyping immune checkpoints prognosis ovarian cancer immune cell infiltration immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.916251/full |
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