Meng Fanjing, Han Xu, Min Zhixue, He Xuehui, Zhu Sha
Key Laboratory of Tumor Immunity, Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Department of Pathology, The Third People's Hospital of Zhengzhou, Zhengzhou, China.
Aging (Albany NY). 2021 Jul 6;13(13):17442-17461. doi: 10.18632/aging.203234.
Metastatic cancer especially bone metastasis (BM) is the lethal end-stage of castration-resistant prostate cancer (CRPC). To understand the possible molecular mechanisms underlying the development of the distant metastasis is of potential clinical value. We sought to identify differentially expressed genes between patient-matched primary and bone metastatic CRPC tumors. Functional enrichment, protein-protein interaction networks, and survival analysis of DEGs were performed. DEGs with a prognostic value considered as candidate genes were evaluated, followed by genetic analysis of tumor infiltrating immune cells based on Wilcoxon test and immunofluorescence identification. Expression profiles analysis showed that 381 overlapping genes were screened as differentially expressed genes (DEGs), of which 16 DEGs were randomly selected to be validated and revealed that most of these genes showed a transcriptional profile similar to that seen in the datasets (Pearson's r = 0.76). Six core genes were found to be involved in regulation of extracellular matrix receptor interaction and chemotactic activity, and four of them were significantly correlated with the survival of PCa patients with bone metastases. Immune infiltration analysis showed that the expressions levels of COL3A1, RAC1, FN1, and SDC2 in CD4+T cells were significantly higher than those in tumor cells, especially regulatory T cell infiltration was significantly increased in BM tumors. We analyzed gene expression signatures specifically associated with the development of bone metastases of CRPC patients. Characterization of genes associated with BM of mCRPC is critical for identification of predictive biomarkers and potential therapeutic targets.
转移性癌症尤其是骨转移（BM）是去势抵抗性前列腺癌（CRPC）的致命终末期。了解远处转移发生的潜在分子机制具有潜在的临床价值。我们试图鉴定患者匹配的原发性和骨转移性CRPC肿瘤之间差异表达的基因。对差异表达基因进行了功能富集、蛋白质-蛋白质相互作用网络分析和生存分析。评估具有预后价值的差异表达基因作为候选基因，随后基于Wilcoxon检验和免疫荧光鉴定对肿瘤浸润免疫细胞进行基因分析。表达谱分析表明，筛选出381个重叠基因作为差异表达基因（DEGs），从中随机选择16个差异表达基因进行验证，结果显示这些基因中的大多数呈现出与数据集中相似的转录谱（Pearson相关系数r = 0.76）。发现6个核心基因参与细胞外基质受体相互作用和趋化活性的调节，其中4个与骨转移前列腺癌患者的生存显著相关。免疫浸润分析表明，CD4+T细胞中COL3A1、RAC1、FN1和SDC2的表达水平显著高于肿瘤细胞，尤其是调节性T细胞浸润在骨转移肿瘤中显著增加。我们分析了与CRPC患者骨转移发生特异性相关的基因表达特征。鉴定与mCRPC骨转移相关的基因对于识别预测性生物标志物和潜在治疗靶点至关重要。
