GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation
<b>Background:</b> Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy...
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2025-07-01
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| author | Congcong Xu Qifeng Zhong Nengfeng Yu Xuqiang Zhang Kefan Yang Hao Liu Ming Cai Yichun Zheng |
| author_facet | Congcong Xu Qifeng Zhong Nengfeng Yu Xuqiang Zhang Kefan Yang Hao Liu Ming Cai Yichun Zheng |
| author_sort | Congcong Xu |
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| description | <b>Background:</b> Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC for the development of tailored anti-tumor immunotherapy. <b>Methods:</b> Consensus clustering analysis was conducted to delineate immune subtypes, while weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine (SVM) algorithms were employed to evaluate the potential efficacy of anti-tumor immunotherapy. Candidate immunotherapy targets were systematically identified through multi-gene panel analyses and subsequently validated using molecular biology assays. A prioritized target emerging from cellular screening was further evaluated for its capacity to potentiate anti-tumor immunity. The therapeutic efficacy of this candidate was rigorously confirmed through a comprehensive suite of immunological experiments. <b>Results:</b> Following systematic screening of five candidate genes (WNT11, FAM181B, GRK5, FSCN1, and ECHS1), GRK5 emerged as a promising therapeutic target for immunotherapy based on its distinct functional and molecular associations with immune evasion mechanisms. Cellular functional assays revealed that GRK5 knockdown significantly attenuated the malignant phenotype of testicular cancer cells, as evidenced by reduced proliferative capacity and invasive potential. Complementary immunological validation established that specific targeting of GRK5 with the selective antagonist GRK5-IN-2 disrupts immune evasion pathways in testicular cancer, as quantified by T-cell-mediated cytotoxicity. <b>Conclusions:</b> These findings position GRK5 as a critical modulator of tumor-immune escape, warranting further preclinical exploration of GRK5-IN-2 as a candidate immunotherapeutic agent. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| series | Biomedicines |
| spelling | doaj-art-5bb7df69660f4f14ae949905eab1b4752025-08-20T04:00:50ZengMDPI AGBiomedicines2227-90592025-07-01137177510.3390/biomedicines13071775GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic ValidationCongcong Xu0Qifeng Zhong1Nengfeng Yu2Xuqiang Zhang3Kefan Yang4Hao Liu5Ming Cai6Yichun Zheng7The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaThe Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310000, ChinaThe Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, ChinaThe Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, ChinaThe Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaThe Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, ChinaThe Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China<b>Background:</b> Personalized anti-tumor therapy that activates the immune response has demonstrated clinical benefits in various cancers. However, its efficacy against testicular cancer (TC) remains uncertain. This study aims to identify suitable patients for anti-tumor immunotherapy and to uncover potential therapeutic targets in TC for the development of tailored anti-tumor immunotherapy. <b>Methods:</b> Consensus clustering analysis was conducted to delineate immune subtypes, while weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine (SVM) algorithms were employed to evaluate the potential efficacy of anti-tumor immunotherapy. Candidate immunotherapy targets were systematically identified through multi-gene panel analyses and subsequently validated using molecular biology assays. A prioritized target emerging from cellular screening was further evaluated for its capacity to potentiate anti-tumor immunity. The therapeutic efficacy of this candidate was rigorously confirmed through a comprehensive suite of immunological experiments. <b>Results:</b> Following systematic screening of five candidate genes (WNT11, FAM181B, GRK5, FSCN1, and ECHS1), GRK5 emerged as a promising therapeutic target for immunotherapy based on its distinct functional and molecular associations with immune evasion mechanisms. Cellular functional assays revealed that GRK5 knockdown significantly attenuated the malignant phenotype of testicular cancer cells, as evidenced by reduced proliferative capacity and invasive potential. Complementary immunological validation established that specific targeting of GRK5 with the selective antagonist GRK5-IN-2 disrupts immune evasion pathways in testicular cancer, as quantified by T-cell-mediated cytotoxicity. <b>Conclusions:</b> These findings position GRK5 as a critical modulator of tumor-immune escape, warranting further preclinical exploration of GRK5-IN-2 as a candidate immunotherapeutic agent.https://www.mdpi.com/2227-9059/13/7/1775testicular cancerpotential therapeutic targetsgenomicsimmune-related cancer subtypespredictive diagnostic model |
| spellingShingle | Congcong Xu Qifeng Zhong Nengfeng Yu Xuqiang Zhang Kefan Yang Hao Liu Ming Cai Yichun Zheng GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation Biomedicines testicular cancer potential therapeutic targets genomics immune-related cancer subtypes predictive diagnostic model |
| title | GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation |
| title_full | GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation |
| title_fullStr | GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation |
| title_full_unstemmed | GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation |
| title_short | GRK5 as a Novel Therapeutic Target for Immune Evasion in Testicular Cancer: Insights from Multi-Omics Analysis and Immunotherapeutic Validation |
| title_sort | grk5 as a novel therapeutic target for immune evasion in testicular cancer insights from multi omics analysis and immunotherapeutic validation |
| topic | testicular cancer potential therapeutic targets genomics immune-related cancer subtypes predictive diagnostic model |
| url | https://www.mdpi.com/2227-9059/13/7/1775 |
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