Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma
Although immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immu...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-11-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1011046/full |
| _version_ | 1828311610412761088 |
|---|---|
| author | Yajun Han Qinqin Cai Xiaolin Xie Shilong Gao Xiwen Fan |
| author_facet | Yajun Han Qinqin Cai Xiaolin Xie Shilong Gao Xiwen Fan |
| author_sort | Yajun Han |
| collection | DOAJ |
| description | Although immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immunogenic cell death (ICD).We constructed an ICD-based prognostic model to predict the prognosis of SKCM patients and the efficacy of immunotherapy. Information on melanoma and normal samples obtained by TCGA and GTEx was stratified by ICD-related genes. The samples were divided into two subtypes according to high and low expression of ICD using an unsupervised clustering method (K-means). Patients with ICD-high subtype showed longer overall survival. We found that the ICD-related differential genes were associated with several cell death and immune-related pathways through GO, KEGG and GSEA. Immunoscore and tumor purity of ICD-associated genes was calculated using ESTIMATE, and ICD-high subtypes had higher immunoscore and lower tumor purity than ICD-low subtypes. Seven ICD-associated genes were obtained by one-way Cox regression and Lasso regression of ICD genes. Risk models were constructed to classify melanoma patients into high- risk and low-risk groups. The expression of ICD-related pivotal genes was lower in the high-risk group than in the low-risk group, and the survival time was significantly higher in the low-risk group than in the high-risk group. We then found that ICD risk characteristics had predictive value for the clinical efficacy of immunotherapy, with higher ICD risk scores in the immunotherapy non-responsive group. Combined with clinicopathological factors, a nomogram was established. the ROC and calibration curves assessed the ability of the nomogram to predict prognosis. We developed a new classification system for SKCM based on the characteristics of ICDs. This stratification has important clinical implications for estimating the prognosis and immunotherapy of SKCM patients. |
| first_indexed | 2024-04-13T16:01:54Z |
| format | Article |
| id | doaj.art-62334495115f4a2892fdb51ed8422c79 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T16:01:54Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-62334495115f4a2892fdb51ed8422c792022-12-22T02:40:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10110461011046Development and validation of prognostic index based on immunogenic cell death-related genes with melanomaYajun Han0Qinqin Cai1Xiaolin Xie2Shilong Gao3Xiwen Fan4Third Clinical Medical College, Xinjiang Medical University, Urumqi, ChinaThird Clinical Medical College, Xinjiang Medical University, Urumqi, ChinaThird Clinical Medical College, Xinjiang Medical University, Urumqi, ChinaThird Clinical Medical College, Xinjiang Medical University, Urumqi, ChinaDepartment of Interventional Medicine, Affiliated Cancer Hospital, Xinjiang Medical University, Urumqi, ChinaAlthough immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immunogenic cell death (ICD).We constructed an ICD-based prognostic model to predict the prognosis of SKCM patients and the efficacy of immunotherapy. Information on melanoma and normal samples obtained by TCGA and GTEx was stratified by ICD-related genes. The samples were divided into two subtypes according to high and low expression of ICD using an unsupervised clustering method (K-means). Patients with ICD-high subtype showed longer overall survival. We found that the ICD-related differential genes were associated with several cell death and immune-related pathways through GO, KEGG and GSEA. Immunoscore and tumor purity of ICD-associated genes was calculated using ESTIMATE, and ICD-high subtypes had higher immunoscore and lower tumor purity than ICD-low subtypes. Seven ICD-associated genes were obtained by one-way Cox regression and Lasso regression of ICD genes. Risk models were constructed to classify melanoma patients into high- risk and low-risk groups. The expression of ICD-related pivotal genes was lower in the high-risk group than in the low-risk group, and the survival time was significantly higher in the low-risk group than in the high-risk group. We then found that ICD risk characteristics had predictive value for the clinical efficacy of immunotherapy, with higher ICD risk scores in the immunotherapy non-responsive group. Combined with clinicopathological factors, a nomogram was established. the ROC and calibration curves assessed the ability of the nomogram to predict prognosis. We developed a new classification system for SKCM based on the characteristics of ICDs. This stratification has important clinical implications for estimating the prognosis and immunotherapy of SKCM patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.1011046/fullimmunogenic cell deathmelanomaprognosistumor microenvionmentimmunotherapy |
| spellingShingle | Yajun Han Qinqin Cai Xiaolin Xie Shilong Gao Xiwen Fan Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma Frontiers in Oncology immunogenic cell death melanoma prognosis tumor microenvionment immunotherapy |
| title | Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma |
| title_full | Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma |
| title_fullStr | Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma |
| title_full_unstemmed | Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma |
| title_short | Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma |
| title_sort | development and validation of prognostic index based on immunogenic cell death related genes with melanoma |
| topic | immunogenic cell death melanoma prognosis tumor microenvionment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1011046/full |
| work_keys_str_mv | AT yajunhan developmentandvalidationofprognosticindexbasedonimmunogeniccelldeathrelatedgeneswithmelanoma AT qinqincai developmentandvalidationofprognosticindexbasedonimmunogeniccelldeathrelatedgeneswithmelanoma AT xiaolinxie developmentandvalidationofprognosticindexbasedonimmunogeniccelldeathrelatedgeneswithmelanoma AT shilonggao developmentandvalidationofprognosticindexbasedonimmunogeniccelldeathrelatedgeneswithmelanoma AT xiwenfan developmentandvalidationofprognosticindexbasedonimmunogeniccelldeathrelatedgeneswithmelanoma |