Wiebringhaus Robert, Pecoraro Matteo, Neubauer Heidi A, Trachtová Karolína, Trimmel Bettina, Wieselberg Maritta, Pencik Jan, Egger Gerda, Krall Christoph, Moriggl Richard, Mann Matthias, Hantusch Brigitte, Kenner Lukas
Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Otolaryngology, University Hospital, LMU Munich, 81377 Munich, Germany.
Cancers (Basel). 2021 Nov 30;13(23):6036. doi: 10.3390/cancers13236036.
We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.
我们旨在通过免疫组织化学分析，并将其与转录组数据以及在一个STAT3非依赖型前列腺癌队列中的生化复发情况相关联，从而在一个由蛋白质组学得出的STAT3低表达线粒体蛋白数据集中，识别侵袭性前列腺癌的新型标志物。对一组前列腺癌患者的福尔马林固定石蜡包埋组织（FFPE）样本进行选择，用于蛋白质组学分析和组织微阵列（TMA）生成。对同一队列进行回顾性数据分析。在STAT3低表达和高表达样本之间，识别出153种差异表达的蛋白质。其中，46种蛋白质与包括氧化磷酸化（OXPHOS）在内的线粒体过程相关，45种蛋白质上调，包括NDUFS1/ATP5O。在一个STAT3非依赖型前列腺癌队列中，通过免疫细胞化学（IHC）证实了NDUFS1/ATP5O的高表达，且其与更早的生化复发（BCR）显著相关。与良性前列腺腺体相比，这两个基因的mRNA表达水平在前列腺上皮内瘤变和前列腺癌中显著更高。在侵袭性前列腺癌中，NDUFS1/ATP5O的水平在mRNA和蛋白质水平均升高。我们的结果提供了证据，表明NDUFS1/ATP5O可用于识别高危前列腺癌患者。
