Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
Cell Death Dis. 2019 Aug 20;10(9):631. doi: 10.1038/s41419-019-1861-1.
Prostate cancer is the second most common cancer in men, for which there are no reliable biomarkers or targeted therapies. Here we demonstrate that elevated levels of Δ133TP53β isoform characterize prostate cancers with immune cell infiltration, particularly T cells and CD163+ macrophages. These cancers are associated with shorter progression-free survival, Gleason scores ≥ 7, and an immunosuppressive environment defined by a higher proportion of PD-1, PD-L1 and colony-stimulating factor 1 receptor (CSF1R) positive cells. Consistent with this, RNA-seq of tumours showed enrichment for pathways associated with immune signalling and cell migration. We further show a role for hypoxia and wild-type p53 in upregulating Δ133TP53 levels. Finally, AUC analysis showed that Δ133TP53β expression level alone predicted aggressive disease with 88% accuracy. Our data identify Δ133TP53β as a highly accurate prognostic factor for aggressive prostate cancer.
前列腺癌是男性中第二常见的癌症，目前尚无可靠的生物标志物或靶向治疗方法。在这里，我们证明高水平的 Δ133TP53β 异构体特征在于具有免疫细胞浸润的前列腺癌，特别是 T 细胞和 CD163+巨噬细胞。这些癌症与无进展生存期更短、Gleason 评分≥7 以及由更高比例的 PD-1、PD-L1 和集落刺激因子 1 受体（CSF1R）阳性细胞定义的免疫抑制环境相关。与此一致的是，肿瘤的 RNA-seq 显示与免疫信号和细胞迁移相关的途径富集。我们进一步表明，缺氧和野生型 p53 在上调 Δ133TP53 水平方面发挥作用。最后，AUC 分析表明，Δ133TP53β 的表达水平单独预测侵袭性疾病的准确率为 88%。我们的数据将 Δ133TP53β 确定为侵袭性前列腺癌的高度准确的预后因素。
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