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SPOCK3 预后标志物影响前列腺癌恶性进展的机制及预后模型的构建。

Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model.

机构信息

Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang West Road, Guangzhou, 510000, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

BMC Cancer. 2023 Aug 11;23(1):741. doi: 10.1186/s12885-023-11151-3.

Abstract

BACKGROUND

SPOCK3 is a secreted extracellular matrix proteoglycan. This study aimed to investigate the effect of SPOCK3 on the malignant progression of prostate cancer and to construct a prognostic model to predict DFS of patients with prostate cancer.

METHODS

Clinical and transcriptome sequencing data for prostate cancer were download from the TCGA and GEO databases. The survival curve showed that SPOCK3 has prognostic significance. GO, KEGG, and GSEA enrichment analysis were used to investigate how SPOCK3 affects the malignant progression of prostate cancer. Based on ESTIMATE and ssGSEA, the relationship between SPOCK3 and immune cell infiltration in prostate cancer tissue was clarified. Univariate and multivariate COX regression analysis was used to identify the independent prognostic factors of prostate cancer OS and to construct a nomogram. The calibration curve and ROC curves were drawn to assess the nomogram's predictive power.

RESULTS

The survival curve revealed that patients in the low-expression group of SPOCK3 had a poor prognosis. According to enrichment analysis, SOPCK3-related genes were enriched in collagen-containing extracellular matrix, PI3K-Akt, and MAPK signaling pathway. ESTIMATE analysis revealed that SPOCK3 expression was positively correlated with the interstitial score, immune score, and ESTIMATE score. The results of ssGSEA analysis revealed that the infiltration levels of Mast cells, NK cells, and B cells were higher in the SPOCK3 high expression group. Cox regression analysis showed that SPOCK3 expression level, T and Gleason score were independent risk factors of patient prognosis, and a nomogram was constructed. The ROC curve showed the AUCs of DFS at 2, 3, and 5 years.

CONCLUSION

SPOCK3 is a protective factor for DFS in prostate cancer patients. SPOCK3 is significantly associated with immune cell infiltration. The prognostic model constructed based on SPOCK3 has excellent predictive performance.

摘要

背景

SPOCK3 是一种分泌型细胞外基质蛋白聚糖。本研究旨在探讨 SPOCK3 对前列腺癌恶性进展的影响,并构建预测前列腺癌患者无复发生存率(DFS)的预后模型。

方法

从 TCGA 和 GEO 数据库下载前列腺癌的临床和转录组测序数据。生存曲线显示 SPOCK3 具有预后意义。GO、KEGG 和 GSEA 富集分析用于研究 SPOCK3 如何影响前列腺癌的恶性进展。基于 ESTIMATE 和 ssGSEA,阐明 SPOCK3 与前列腺癌组织中免疫细胞浸润的关系。单因素和多因素 COX 回归分析用于确定前列腺癌 OS 的独立预后因素,并构建列线图。绘制校准曲线和 ROC 曲线以评估列线图的预测能力。

结果

生存曲线显示 SPOCK3 低表达组的患者预后较差。根据富集分析,与 SOPCK3 相关的基因富集在含有胶原蛋白的细胞外基质、PI3K-Akt 和 MAPK 信号通路中。ESTIMATE 分析显示 SPOCK3 表达与间质评分、免疫评分和 ESTIMATE 评分呈正相关。ssGSEA 分析结果表明,SPOCK3 高表达组 Mast 细胞、NK 细胞和 B 细胞的浸润水平较高。Cox 回归分析显示 SPOCK3 表达水平、T 分期和 Gleason 评分是患者预后的独立危险因素,并构建了列线图。ROC 曲线显示 DFS 在 2、3 和 5 年的 AUC。

结论

SPOCK3 是前列腺癌患者 DFS 的保护因素。SPOCK3 与免疫细胞浸润显著相关。基于 SPOCK3 构建的预后模型具有优异的预测性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0086/10416445/2ba87f46515a/12885_2023_11151_Fig1_HTML.jpg

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