Bao Yizhong, Ni Yixiu, Zhang Aokang, Chen Jun
Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310013, Zhejiang Province, China.
School of Medicine, Zhejiang University, Hangzhou, 310013, Zhejiang Province, China.
J Cancer. 2024 Oct 21;15(20):6545-6564. doi: 10.7150/jca.101100. eCollection 2024.
Prostate cancer (PCa) is a malignancy that affects men and is characterized by metastasis and high rates of morbidity. The objective of this study was to explore novel PCa biomarker with potential diagnostic and therapeutic value and relationships between it and tumor immunity and development. A total of 32 key genes were screened out via LASSO based upon 188 intersection genes obtained from WGCNA and DEGs analysis in GSE32571, and PPP1R14B was further identified by COX regression based on the TCGA database and validated by qRT-PCR. Although it has been reported that PPP1R14B may have a certain correlation with the prognosis of uterine corpus endometrial carcinoma, breast cancer and gastrointestinal cancer, there are none of studies about correlation between PPP1R14B and PCa. Predictive ability analysis showed that PPP1R14B had greatly predictive values in occurrence and prognosis of PCa. Immune analysis revealed that overexpression of PPP1R14B was related to the increase of ALKBH2, UCK2, RAC3 and RAB17 and the decrease of CD40, DKK3, COL17A1 and PGRMC1, which would result in downregulation of plasma cells, upregulation of T regulatory cells and disorder of macrophage proportion to suppress adaptive immune directed against PCa. GSEA analysis showed that PPP1R14B, as an inhibitor of PP1, its overexpression was mainly involved in regulating pathways associated with MYC, E2F, PFN1 and so on, which was participated in the regulation of immune factors such as CD40, RAC3, COL17A, DKK3, as well as biological processes such as proliferation and migration. Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.
前列腺癌(PCa)是一种影响男性的恶性肿瘤,其特征为转移和高发病率。本研究的目的是探索具有潜在诊断和治疗价值的新型PCa生物标志物及其与肿瘤免疫和发展之间的关系。基于从WGCNA和GSE32571中的差异表达基因(DEGs)分析获得的188个交集基因,通过LASSO筛选出总共32个关键基因,并基于TCGA数据库通过COX回归进一步鉴定出PPP1R14B,并通过qRT-PCR进行验证。尽管已有报道称PPP1R14B可能与子宫体子宫内膜癌、乳腺癌和胃肠道癌的预后有一定相关性,但尚无关于PPP1R14B与PCa相关性的研究。预测能力分析表明,PPP1R14B在PCa的发生和预后方面具有很大的预测价值。免疫分析显示,PPP1R14B的过表达与ALKBH2、UCK2、RAC3和RAB17的增加以及CD40、DKK3、COL17A1和PGRMC1的减少有关,这将导致浆细胞下调、调节性T细胞上调以及巨噬细胞比例紊乱,从而抑制针对PCa的适应性免疫。基因集富集分析(GSEA)表明,PPP1R14B作为PP1的抑制剂,其过表达主要参与调节与MYC、E2F、PFN1等相关的途径,这些途径参与调节免疫因子如CD40、RAC3、COL17A、DKK3以及增殖和迁移等生物学过程。PPP1R14B表达较高的患者对药物司美替尼和伏立诺他、泽布勒林、阿扎胞苷和VER155008反应更敏感。总之,PPP1R14B是PCa潜在的诊断和预后生物标志物,其高表达与肿瘤免疫抑制、增殖和迁移密切相关,为PCa的药物治疗和免疫治疗提供了新靶点。