细胞衰老在癌症领域越来越受欢迎。衰老相关分泌表型（SASP）在炎症微环境、组织再生或破坏、衰老传播和恶性转化的发展中起到双重作用。本研究通过全面的生物信息学分析和荟萃分析，利用经过实验证实的SASP基因，发现了前列腺癌（PCa）患者的有害和有益亚型及预后指数。我们确定了差异表达和与预后相关的SASP基因，并使用它们构建了两种分子亚型和风险评分。其他两个外部队列用于验证上述亚型和风险评分的预后效果，并进行了荟萃分析。此外，我们还评估了功能分析、肿瘤干性和异质性以及肿瘤微环境。我们使用R 3.6.3软件及其适用的包完成了分析工作。荟萃分析使用Stata 14.0软件进行。通过多变量Cox回归分析和一致性聚类分析，我们使用VGF、IGFBP3和ANG在TCGA队列中建立了有害和有益亚型，并通过其他两个独立队列进行了验证。荟萃分析显示有害SASP组与有益SASP组相比，在生化复发（BCR）风险上具有显著高于（HR：2.48）。此外，我们还基于这些基因构建和验证了风险评分，以更好地指导临床实践。在有害SASP组中高度富集了DNA修复、MYC靶基因、氧化磷酸化、蛋白酶体和核糖体。与有益SASP组相比，有害SASP组的B细胞、CD8+ T细胞、同源重组缺陷、等位基因丧失、微卫星不稳定、纯度、肿瘤突变负荷、mRNAsi、差异甲基化位点和表观调控的RNA表达水平显著增加。有害SASP组和有益SASP组之间的top突变基因分别为SPOP、FOXA1、KMT2C、APC、BSN、DNAH17、MYH6、EPPK1、ZNF536和ZC3H13，具有统计学意义。从SASP的角度来看，我们发现与PCa患者的BCR生存密切相关的有害和有益肿瘤亚型，这对于未来PCa领域的研究可能非常重要。© 2023. Springer Science+Business Media, LLC.

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.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.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.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.© 2023. Springer Science+Business Media, LLC.