Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy
Abstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and ma...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-08-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-023-00777-1 |
| _version_ | 1797452156047982592 |
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| author | Dechao Feng Jie Wang Dengxiong Li Ruicheng Wu Wuran Wei Chi Zhang |
| author_facet | Dechao Feng Jie Wang Dengxiong Li Ruicheng Wu Wuran Wei Chi Zhang |
| author_sort | Dechao Feng |
| collection | DOAJ |
| description | Abstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes. Methods We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0. Results Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance. Conclusions From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa. |
| first_indexed | 2024-03-09T15:04:41Z |
| format | Article |
| id | doaj.art-2d512e736cd44491a442ba2ae5be3edb |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-03-09T15:04:41Z |
| publishDate | 2023-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-2d512e736cd44491a442ba2ae5be3edb2023-11-26T13:43:29ZengSpringerDiscover Oncology2730-60112023-08-0114111410.1007/s12672-023-00777-1Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomyDechao Feng0Jie Wang1Dengxiong Li2Ruicheng Wu3Wuran Wei4Chi Zhang5Department of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Urology, Institute of Urology, West China Hospital, Sichuan UniversityDepartment of Rehabilitation, The Affiliated Hospital of Southwest Medical UniversityAbstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes. Methods We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0. Results Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance. Conclusions From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa.https://doi.org/10.1007/s12672-023-00777-1Prostate cancerBiochemical recurrenceSenescence-associated secretory phenotypeMolecular subtypesMeta-analysis |
| spellingShingle | Dechao Feng Jie Wang Dengxiong Li Ruicheng Wu Wuran Wei Chi Zhang Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy Discover Oncology Prostate cancer Biochemical recurrence Senescence-associated secretory phenotype Molecular subtypes Meta-analysis |
| title | Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| title_full | Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| title_fullStr | Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| title_full_unstemmed | Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| title_short | Senescence-associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| title_sort | senescence associated secretory phenotype constructed detrimental and beneficial subtypes and prognostic index for prostate cancer patients undergoing radical prostatectomy |
| topic | Prostate cancer Biochemical recurrence Senescence-associated secretory phenotype Molecular subtypes Meta-analysis |
| url | https://doi.org/10.1007/s12672-023-00777-1 |
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