Liang Xiaoxing, Huang Renlun, Ping Xinyue, Deng Wei, Xiang Songtao, Wang Zhichao, Cao Jiadong
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Urology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Transl Cancer Res. 2024 Aug 31;13(8):3996-4009. doi: 10.21037/tcr-23-2100. Epub 2024 Aug 27.
Metastasis worsens prostate cancer (PCa) prognosis, with the immunosuppressive microenvironment playing a key role in bone metastasis. This study aimed to investigate how an immunosuppressive environment promotes PCa metastasis and worsens prognosis of patients with PCa.
Candidate oncogenes were identified through analysis of the Gene Expression Omnibus (GEO) database. A prognostic model was developed for the purpose of identifying target genes. A single-cell RNA sequencing data from GEO database was used to analyze the localization of target genes in the tumor microenvironment. A pan-cancer analysis was conducted to study the cancer-causing potential of target genes across different types of tumors.
Fifty-one genes were found to be differentially expressed in bone metastasis compared to non-metastatic PCa, with CKS2 identified as the most significant gene associated with poor prognosis. CKS2 was shown to be linked to an immunosuppressive microenvironment and osteoclastic bone metastases, as shown by its negative correlation with immune cell infiltration and osteoblast-related gene expression. Moreover, CKS2 was found in immunosuppressive cells and was linked to bone metastasis in PCa. It was also overexpressed in different types of tumors, making it as an oncogenic gene.
This research offers a new perspective on the potential utility of CKS2 as a therapeutic target for the prevention of metastatic PCa.
转移会恶化前列腺癌(PCa)的预后,免疫抑制微环境在骨转移中起关键作用。本研究旨在探讨免疫抑制环境如何促进PCa转移并恶化PCa患者的预后。
通过分析基因表达综合数据库(GEO)来鉴定候选癌基因。为了识别靶基因,构建了一个预后模型。利用来自GEO数据库的单细胞RNA测序数据来分析靶基因在肿瘤微环境中的定位。进行泛癌分析以研究靶基因在不同类型肿瘤中的致癌潜力。
与非转移性PCa相比,发现有51个基因在骨转移中差异表达,其中CKS2被确定为与预后不良相关的最显著基因。CKS2与免疫抑制微环境和破骨性骨转移有关,这表现为它与免疫细胞浸润和成骨细胞相关基因表达呈负相关。此外,CKS2在免疫抑制细胞中被发现,并且与PCa中的骨转移有关。它在不同类型的肿瘤中也过表达,使其成为一个致癌基因。
本研究为CKS2作为预防转移性PCa的治疗靶点的潜在效用提供了新的视角。