前列腺癌惡性進展的預後標誌物SPOCK3的作用機制及預後模型構建的研究
Mechanism of prognostic marker SPOCK3 affecting malignant progression of prostate cancer and construction of prognostic model.
发表日期:2023 Aug 11
作者:
Jiawen Luo, Cong Lai, Xiaoting Xu, Juanyi Shi, Jintao Hu, Kaixuan Guo, Yelisudan Mulati, Yunfei Xiao, Degeng Kong, Cheng Liu, Kewei Xu
来源:
Epigenetics & Chromatin
摘要:
SPOCK3是一种分泌的细胞外基质蛋白多聚糖。本研究旨在研究SPOCK3对前列腺癌恶性进展的影响,并构建一个预测前列腺癌患者DFS的预后模型。从TCGA和GEO数据库中下载了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。利用GO、KEGG和GSEA富集分析研究SPOCK3如何影响前列腺癌的恶性进展。基于ESTIMATE和ssGSEA,阐明了SPOCK3与前列腺癌组织中免疫细胞浸润的关系。使用单变量和多变量COX回归分析来确定前列腺癌OS的独立预后因素并构建预测模型。绘制校准曲线和ROC曲线评估预测模型的预测能力。生存曲线显示SPOCK3低表达组的患者预后较差。根据富集分析,SPOCK3相关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分析结果显示,在SPOCK3高表达组中,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和Gleason评分是患者预后的独立风险因素,并构建了预测模型。ROC曲线显示DFS在2年、3年和5年时的AUC值。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良好的预测性能。© 2023. BioMed Central Ltd., part of Springer Nature.
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.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.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.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.© 2023. BioMed Central Ltd., part of Springer Nature.