State Key Laboratory of Oncogenes and Related Genes, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.
Cancer Med. 2021 Aug;10(15):5358-5374. doi: 10.1002/cam4.4063. Epub 2021 Jun 15.
Tumor-infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation.
Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features.
We categorized PRAD patients into high and low-level clusters based on immune infiltration phenotypes. The patients in the high-level clusters had worse survival than their low-level counterparts. Gene set enrichment analysis indicated that both anti- and pro-tumor terms were enriched in high-level cluster. Moreover, we identified a positive correlation between anti- and pro-tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high-level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high-risk PRAD patients with poor prognosis from low-risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice.
Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features.
浸润肿瘤的免疫细胞参与前列腺腺癌（PRAD）的发生和发展。然而，免疫浸润如何影响 PRAD 的发展及其临床表现尚不完全清楚。
在此，我们基于转录组谱、甲基化谱、体细胞突变和拷贝数变异，研究了 PRAD 中的免疫浸润表型。我们还开发了一种免疫预后模型（IPM）来识别不良预后。为了验证该模型，我们对 PRAD 样本进行了免疫组织化学染色。此外，我们构建了一个列线图，将免疫浸润和其他临床特征纳入 PRAD 患者的生存评估。
我们根据免疫浸润表型将 PRAD 患者分为高和低水平聚类。高水平聚类的患者比低水平聚类的患者预后更差。基因集富集分析表明，在高水平聚类中富集了抗肿瘤和促肿瘤术语。此外，我们发现 PRAD 微环境中抗肿瘤和促肿瘤免疫细胞之间存在正相关。值得注意的是，体细胞突变分析表明高水平聚类的患者具有更高的 KMT2D、HSPA8、CHD7 和 MAP1A 的体细胞突变负担。此外，我们开发了一种具有稳健预测能力的 IPM。该模型可以区分训练集和另外三个独立验证数据集中预后不良的高危 PRAD 患者和低危 PRAD 患者。此外，我们构建了一个纳入 Gleason 评分、病理 T 分期和 IPM 的列线图，用于预测 PRAD 患者的预后，该列线图具有稳健的预测能力，可能有助于临床实践。
我们的工作表明，免疫浸润表型与 PRAD 患者的不良预后密切相关，并强调了 IPM 识别不良肿瘤特征的潜力。
