Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment
Abstract Background Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis an...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-024-01672-3 |
| _version_ | 1827328124462825472 |
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| author | Bintao Hu Xi Zhang Shiqing Zhu Chengwei Wang Zhiyao Deng Tao Wang Yue Wu |
| author_facet | Bintao Hu Xi Zhang Shiqing Zhu Chengwei Wang Zhiyao Deng Tao Wang Yue Wu |
| author_sort | Bintao Hu |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis. Methods In this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RT‒qPCR. Results PCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan–Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples. Conclusions The MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients. |
| first_indexed | 2024-03-07T15:13:23Z |
| format | Article |
| id | doaj.art-c0280c85b9b64707b88b483406a3733e |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-07T15:13:23Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-c0280c85b9b64707b88b483406a3733e2024-03-05T18:04:05ZengBMCEuropean Journal of Medical Research2047-783X2024-01-0129111910.1186/s40001-024-01672-3Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironmentBintao Hu0Xi Zhang1Shiqing Zhu2Chengwei Wang3Zhiyao Deng4Tao Wang5Yue Wu6Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologySchool of Nursing, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis. Methods In this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RT‒qPCR. Results PCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan–Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples. Conclusions The MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients.https://doi.org/10.1186/s40001-024-01672-3Prostate cancerImmune microenvironmentBiochemical recurrenceImmune geneMetabolic genesPrognostic signature |
| spellingShingle | Bintao Hu Xi Zhang Shiqing Zhu Chengwei Wang Zhiyao Deng Tao Wang Yue Wu Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment European Journal of Medical Research Prostate cancer Immune microenvironment Biochemical recurrence Immune gene Metabolic genes Prognostic signature |
| title | Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| title_full | Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| title_fullStr | Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| title_full_unstemmed | Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| title_short | Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| title_sort | identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment |
| topic | Prostate cancer Immune microenvironment Biochemical recurrence Immune gene Metabolic genes Prognostic signature |
| url | https://doi.org/10.1186/s40001-024-01672-3 |
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