Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Aging (Albany NY). 2020 Nov 10;12(22):22776-22793. doi: 10.18632/aging.103921.
In this study, we constructed a model using a Cox proportional hazards model based on the expression of eight immune-related genes that were associated with prognosis in prostate cancer: EDNRB, ANGPTL2, TNFSF15, TNFRSF10D, EDN2, BMP2, NLRP14, and PLK1. We then identified associations between risk scores calculated with the model, tumor microenvironment characteristics, and immune cell infiltration. Prostate cancer patients in the high score group had poorer prognoses, and validation with the external GSE54460 dataset confirmed that the scoring model predicted biochemical recurrence with AUC values of 0.749 at 1 year, 0.804 at 3 years, and 0.774 at 5 years. Proportions of infiltrated M2 macrophages and regulatory T cells were increased in the high risk group, while CD8 T cells were increased in the low risk group. Network analysis revealed that PLK1 may be a key regulator of the immune-suppressive microenvironment in prostate cancer. Double immunofluorescence labeling of a prostate cancer tissue microarray indicated that PLK1 expression correlated positively with numbers of infiltrating macrophages. These results indicate that an immune- related, gene-based risk score effectively reflects immune microenvironment characteristics and predicts prognosis in prostate cancer.
在这项研究中,我们构建了一个基于与前列腺癌预后相关的 8 个免疫相关基因表达的 Cox 比例风险模型:EDNRB、ANGPTL2、TNFSF15、TNFRSF10D、EDN2、BMP2、NLRP14 和 PLK1。然后,我们确定了模型计算的风险评分与肿瘤微环境特征和免疫细胞浸润之间的关联。高评分组的前列腺癌患者预后较差,外部 GSE54460 数据集的验证表明,评分模型预测生化复发的 AUC 值在 1 年时为 0.749,在 3 年时为 0.804,在 5 年时为 0.774。高风险组中浸润的 M2 巨噬细胞和调节性 T 细胞的比例增加,而低风险组中 CD8 T 细胞增加。网络分析表明,PLK1 可能是前列腺癌免疫抑制微环境的关键调节因子。前列腺癌组织微阵列的双重免疫荧光标记表明,PLK1 表达与浸润巨噬细胞数量呈正相关。这些结果表明,基于免疫相关基因的风险评分可有效反映免疫微环境特征,并预测前列腺癌的预后。