Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma
Background: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival.Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients...
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| Format: | Article |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00664/full |
| _version_ | 1828789175228301312 |
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| author | Wei Li Lin Xu Jun Han Kefei Yuan Hong Wu |
| author_facet | Wei Li Lin Xu Jun Han Kefei Yuan Hong Wu |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Background: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival.Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients in the TCGA database were included in this study. Immune features were assessed by immunohistochemical staining or CIBERSORT method. We constructed prognostic classifiers by LASSO COX analyses in the TCGA cohort, which identified five features out of the 22 types of immune cells.Results: The formulas based on the immunohistochemical staining are as follows: ISOS = 0.648* Macrophagestromal + 0.444*Neutrophilsstromal + 0.218*Tregsstromal – 0.703*Memory T cellsstromal; ISDFS = 0.285*B cellsstromal + 0.494*Neutrophilsstromal + 0.431*Tregsstromal – 0.736*Memory T cellsstromal. We classified HCC patients into immune type A subgroup (IS-A) and type B subgroup (IS-B) based on immune scores. The immune type was an independent prognostic indicator for disease-free survival (DFS) and overall survival (OS) in both testing and validation cohorts. Two nomograms (for OS and DFS) that integrated the immune type and clinicopathologic risk factors also showed good predictive accuracy and discriminatory power. IS-A group was correlated with higher immune checkpoint molecule expression. In addition, patients with IS-A and IS-B had distinct mutation signature.Conclusion: The immune types could predict survival and recurrence of HCC effectively. In addition, the immunosuppressive pathways and mutation signature are distinct between two immune types. |
| first_indexed | 2024-12-12T01:06:37Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T01:06:37Z |
| publishDate | 2019-08-01 |
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| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4383a17c7a334064a993a10623bd17c12022-12-22T00:43:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-08-01910.3389/fonc.2019.00664469414Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular CarcinomaWei Li0Lin Xu1Jun Han2Kefei Yuan3Hong Wu4Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, ChinaDepartment of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, ChinaDepartment of Critical Care Medicine, Sichuan Provincial Hospital for Women and Children, Chengdu, ChinaDepartment of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, ChinaDepartment of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, ChinaBackground: The immune landscape of hepatocellular carcinoma (HCC) is heterogeneous. This study aims to develop the immune type which could improve predictive value of HCC survival.Methods: A total of 208 HCC patients in the testing cohort, 112 patients in the validation cohort and 365 HCC patients in the TCGA database were included in this study. Immune features were assessed by immunohistochemical staining or CIBERSORT method. We constructed prognostic classifiers by LASSO COX analyses in the TCGA cohort, which identified five features out of the 22 types of immune cells.Results: The formulas based on the immunohistochemical staining are as follows: ISOS = 0.648* Macrophagestromal + 0.444*Neutrophilsstromal + 0.218*Tregsstromal – 0.703*Memory T cellsstromal; ISDFS = 0.285*B cellsstromal + 0.494*Neutrophilsstromal + 0.431*Tregsstromal – 0.736*Memory T cellsstromal. We classified HCC patients into immune type A subgroup (IS-A) and type B subgroup (IS-B) based on immune scores. The immune type was an independent prognostic indicator for disease-free survival (DFS) and overall survival (OS) in both testing and validation cohorts. Two nomograms (for OS and DFS) that integrated the immune type and clinicopathologic risk factors also showed good predictive accuracy and discriminatory power. IS-A group was correlated with higher immune checkpoint molecule expression. In addition, patients with IS-A and IS-B had distinct mutation signature.Conclusion: The immune types could predict survival and recurrence of HCC effectively. In addition, the immunosuppressive pathways and mutation signature are distinct between two immune types.https://www.frontiersin.org/article/10.3389/fonc.2019.00664/fullstromal immunotypehepatocellular carcinomaprognosisLASSO COXTCGA |
| spellingShingle | Wei Li Lin Xu Jun Han Kefei Yuan Hong Wu Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma Frontiers in Oncology stromal immunotype hepatocellular carcinoma prognosis LASSO COX TCGA |
| title | Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma |
| title_full | Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma |
| title_fullStr | Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma |
| title_full_unstemmed | Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma |
| title_short | Identification and Validation of Tumor Stromal Immunotype in Patients With Hepatocellular Carcinoma |
| title_sort | identification and validation of tumor stromal immunotype in patients with hepatocellular carcinoma |
| topic | stromal immunotype hepatocellular carcinoma prognosis LASSO COX TCGA |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00664/full |
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