Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma
Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all pote...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-02966-y |
| _version_ | 1797795454580162560 |
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| author | Ganghua Zhang Zhijing Yin Jianing Fang Anshan Wu Guanjun Chen Ke Cao |
| author_facet | Ganghua Zhang Zhijing Yin Jianing Fang Anshan Wu Guanjun Chen Ke Cao |
| author_sort | Ganghua Zhang |
| collection | DOAJ |
| description | Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. Methods CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. Results Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. Conclusions In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens. |
| first_indexed | 2024-03-13T03:19:09Z |
| format | Article |
| id | doaj.art-6a59387f0974456694caaf07ac3dc4f5 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-13T03:19:09Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-6a59387f0974456694caaf07ac3dc4f52023-06-25T11:29:51ZengBMCCancer Cell International1475-28672023-06-0123112810.1186/s12935-023-02966-yConstruction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinomaGanghua Zhang0Zhijing Yin1Jianing Fang2Anshan Wu3Guanjun Chen4Ke Cao5Department of Oncology, Third Xiangya Hospital, Central South UniversityDepartment of Oncology, Third Xiangya Hospital, Central South UniversityDepartment of Oncology, Third Xiangya Hospital, Central South UniversityZhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South UniversityDepartment of Oncology, Third Xiangya Hospital, Central South UniversityDepartment of Oncology, Third Xiangya Hospital, Central South UniversityAbstract Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. Methods CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. Results Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. Conclusions In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.https://doi.org/10.1186/s12935-023-02966-yUterine corpus endometrial carcinomaCD8+ T cellImmune responseGene mutationNIRS |
| spellingShingle | Ganghua Zhang Zhijing Yin Jianing Fang Anshan Wu Guanjun Chen Ke Cao Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma Cancer Cell International Uterine corpus endometrial carcinoma CD8+ T cell Immune response Gene mutation NIRS |
| title | Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma |
| title_full | Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma |
| title_fullStr | Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma |
| title_full_unstemmed | Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma |
| title_short | Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma |
| title_sort | construction of the novel immune risk scoring system related to cd8 t cells in uterine corpus endometrial carcinoma |
| topic | Uterine corpus endometrial carcinoma CD8+ T cell Immune response Gene mutation NIRS |
| url | https://doi.org/10.1186/s12935-023-02966-y |
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