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Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′‐triiodo‐l‐thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ‐Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage‐specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3‐ and androgen‐mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth., What's new? Thyroid hormones may play a role in the progression of prostate cancer (PCa). In this study, the authors found that PCa cells had decreased expression of the thyroid‐hormone‐binding protein μ‐Crystallin (CRYM). Lower CRYM was also associated with poor prognosis in men with PCa. In addition, CRYM inhibited thyroid‐hormone and androgen signaling, as well as 18F‐fluoromethylcholine uptake by PCa cells. These results suggest that CRYM may act as a novel antagonist against factors that fuel PCa progression, and therefore thyroid signalling may offer a new therapeutic target in slowing aggressive prostate cancer.

The indoor environment that surrounds us and the elements in it affect not only our mood but also the air quality. Vegetation elements are currently more popular, especially for their aesthetic value but also because of the fact that they affect the physical parameters of the indoor environment such as temperature and humidity. Water elements are a similar example. The presented paper combines these two elements to achieve the best possible level of thermal comfort. Experimental verification of the influence of the living wall on air temperature and humidity took place during the heating season in the city of Brno in the space of the university, while three scenarios were created: the effect of the living wall in a semi-open space, an enclosed space, and a space with a water wall with regulated water temperature. The potential of the water wall is determined based on experimental verification in laboratory conditions. The results show that the synergy of the living and water wall in the indoor space may eliminate the risk of too-low humidity during the heating season.

Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co‐expression network of transcriptomics data in addition to laser‐microdissected proteomics from human and murine prostate FFPE samples. We show up‐regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up‐regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis., Transcriptomic and proteomic analyses in prostate cancer (PCa) reveal high TCA/OXPHOS activity and low PDK4 expression in low STAT3 tumors. PDK4 is a promising independent predictor of biochemical recurrence in PCa.

Metabolic rewiring and redox balance play pivotal roles in cancer. Cellular senescence is a barrier for tumorigenesis circumvented in cancer cells by poorly understood mechanisms. We report a multi-enzymatic complex that reprograms NAD metabolism by transferring reducing equivalents from NADH to NADP+. This hydride transfer complex (HTC) is assembled by malate dehydrogenase 1, malic enzyme 1, and cytosolic pyruvate carboxylase. HTC is found in phase-separated bodies in the cytosol of cancer or hypoxic cells and can be assembled in vitro with recombinant proteins. HTC is repressed in senescent cells but induced by p53 inactivation. HTC enzymes are highly expressed in mouse and human prostate cancer models, and their inactivation triggers senescence. Exogenous expression of HTC is sufficient to bypass senescence, rescue cells from complex I inhibitors, and cooperate with oncogenic RAS to transform primary cells. Altogether, we provide evidence for a new multi-enzymatic complex that reprograms metabolism and overcomes cellular senescence.

STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that expressed either human STAT5B or STAT5BN642H in the hematopoietic compartment. While STAT5B-expressing mice lacked a hematopoietic phenotype, the STAT5BN642H-expressing mice rapidly developed T cell neoplasms. Neoplasia manifested as transplantable CD8+ lymphoma or leukemia, indicating that the STAT5BN642H mutation drives cancer development. Persistent and enhanced levels of STAT5BN642H tyrosine phosphorylation in transformed CD8+ T cells led to profound changes in gene expression that were accompanied by alterations in DNA methylation at potential histone methyltransferase EZH2-binding sites. Aurora kinase genes were enriched in STAT5BN642H-expressing CD8+ T cells, which were exquisitely sensitive to JAK and Aurora kinase inhibitors. Together, our data suggest that JAK and Aurora kinase inhibitors should be further explored as potential therapeutics for lymphoma and leukemia patients with the STAT5BN642H mutation who respond poorly to conventional chemotherapy.

Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen deprivation remain poorly described, despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild-type (WT) mouse prostates a rare population of luminal progenitor cells that we called LSCmed according to their FACS profile (Lin- /Sca-1+ /CD49fmed ). Here, we investigated the prevalence and castration resistance of LSCmed in various mouse models of prostate tumourigenesis (Pb-PRL, Ptenpc-/- , and Hi-Myc mice). LSCmed prevalence is low (∼8%, similar to WT) in Hi-Myc mice, where prostatic androgen receptor signalling is unaltered, but is significantly higher in the two other models, where androgen receptor signalling is decreased, rising up to more than 80% in Ptenpc-/- prostates. LSCmed tolerate androgen deprivation and persist or are enriched 2-3 weeks after castration. The tumour-initiating properties of LSCmed from Ptenpc-/- mice were demonstrated by regeneration of tumours in vivo. Transcriptomic analysis revealed that LSCmed represent a unique cell entity as their gene expression profile is different from luminal and basal/stem cells, but shares markers of each. Their intrinsic androgen signalling is markedly decreased, explaining why LSCmed tolerate androgen deprivation. This also illuminates why Ptenpc-/- tumours are castration-resistant since LSCmed represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSCmed on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSCmed in various mouse prostate specimens. In castrated Ptenpc-/- prostates, there was significant proliferation of CK4+ cells, further demonstrating their key role in castration-resistant prostate cancer progression. Taken together, this study identifies LSCmed as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate-resistant prostate cancer. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3’-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidence indicates a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRa/TRb) in target tissues. We show in this study that low CRYM expression levels in PCa patient samples are associated with early BCR and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in PET/MRI imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3 and androgen-mediated signalling. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.HighlightsThyroid and androgen hormone driven pathways in prostate cancer (PCa) are antagonized by μ- Crystallin (CRYM).[18F]fluoromethylcholine uptake and prognostic values in PCa correlate with CRYM protein levels.Reduced CRYM expression predicts early biochemical recurrence (BCR) in PCa patients.

Information communication technologies bring the revolution into all business sectors, and transportation sector is not an exception. Ticketing system has changed from traditional to intelligent, which provides information and service to the consumer. In developed countries such systems are implemented and operate successfully, while in the developing countries electronic ticketing and other similar innovative solutions face specific challenges. These challenges are related to information era and changes in consumer behaviour, caused by the development of information and communication technologies. In these new conditions the motives of consumers to choose electronic ticketing has become an extremely important factor of success. Lack of integrity of consumer behaviour and technology acceptance (electronic ticketing in particular) was identified in previous scientific research, especially taking into consideration recent conditions of developing countries. The aim of this article is to evaluate the consumers’ behaviour and acceptance of intelligent systems, such as electronic ticketing, in order to identify factors, influencing and encouraging the customers to use electronic ticketing systems. In this study extended technology acceptance model with trust element was used to measure the consumer behaviour. The sample for this research has been taken from China and Pakistan populations and consists of 432 participants from both countries.

Prostate cancer (PCa) has a broad spectrum of clinical behaviour, hence biomarkers are urgently needed for risk stratification. We previously described the protective effect of STAT3 in a prostate cancer mouse model. By utilizing a gene co-expression network in addition to laser microdissected proteomics from human and murine prostate FFPE samples, we describe STAT3-induced downregulation of the TCA cycle/OXPHOS in PCa on transcriptomic and proteomic level. We identify pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging and PSA level. Furthermore, PDK4 expression is causally linked to type 2 diabetes mellitus, which is known to have a protective effect on PCa. We conclude that this effect is related to PDK4 expression and that PDK4 loss could serve as a biomarker for PCa with dismal prognosis.

Since publication of the article, the authors became aware that Figure 6(A,D) contained errors in the bands and loading controls. The newly compiled Figure 6A and 6D is given below.

The article is focused on simulation of moisture transfer in wood of norway spruce (Picea abies L.). Experimental specimen was exposed to the northern climatic conditions in Lund University, Sweden. The moisture content of wood was measured 10 mm from the surface for nearly three years. The ABAQUS program was used for numerical modelling of moisture transfer simulation in 3D. The surface sorption of wood was simulated using user defined subroutine DFLUX developed by VTT Research Centre of Finland Ltd. for the needs of European Project Durable Timber Bridges. Climate data for the analysis was used from in-situ measurement nearby realized by weather station. The temperature, relative humidity of the air and precipitation data was record each hour. Numerical analysis took into account influence of rain effect on different parts of specimen surface. Článek je zaměřen na simulaci přenosu vlhkosti v dřevěném smrku (Picea abies L.). Experimentální vzorek byl vystaven severním klimatickým podmínkám na univerzitě Lund ve Švédsku. Obsah vlhkosti dřeva byl měřen 10 mm od povrchu téměř tři roky. Program ABAQUS byl použit pro numerické modelování simulace přenosu vlhkosti ve 3D. Povrchová sorpce dřeva byla simulována pomocí uživatelsky definovaného podprogramu DFLUX vyvinutého firmou VTT Research Centre of Finland Ltd. pro potřeby evropských projektů Durable Timber Bridge. Klimatické údaje pro analýzu byly použity z in-situ měření v blízkosti realizované meteorologickou stanicí. Teplota, relativní vlhkost vzduchu a údaje o srážení byly zaznamenávány každou hodinu. Numerická analýza zohlednila vliv dešťového efektu na různé části povrchu vzorku.

Introduction Prostate cancer (PCa) is the most frequently diagnosed malignancy in men and ranks as the third leading cause of cancer-related death in Western civilization. There is an urgent need to provide diagnostic tools able to reliably stratify aggressive from slow progressing tumours. As a result, over-diagnosis of PCa remains a prevalent issue and patients frequently suffer from severe side effects following therapeutic intervention. Recently, whole-exome sequencing has identified the MLL family member KMT2C amongst the most frequently mutated genes in human prostate cancer. However, the exact role of this histone lysine methyltransferase in tumorigenesis remains elusive. In this study we aim to investigate the contribution of the methyltransferase activity of Kmt2c to prostate tumorigenesis using a Pten-deficient mouse model of PCa. Material and methods We have developed a mouse model with a double deletion of the tumour suppressor Pten and the methyltransferase domain of Kmt2c in the prostate epithelium (PtenKmt2cPE-/-). Mice were sacrificed at 19 weeks of age and prostate tissue was analysed according to size, morphology and selected markers involved in tumorigenesis in comparison to Pten-deficient control mice (PtenPE-/-). To establish human relevance, we investigated the correlation of KMT2C expression to biochemical recurrence (BCR) and exploited publicly available databases to gain insight from the mutational frequency spectrum of KMT2C in PCa. Results and discussions Deletion of the Kmt2c methyltransferase activity (PtenKmt2cPE-/-) resulted in severely reduced life expectancy, increased tumour size and weight accompanied by a more aggressive histopathological morphology. PtenKmt2cPE-/- tumours showed increased proliferation rates and a deregulation of several histone marks. In a dataset of human PCa patients we found that low expression as well as truncating mutations of KMT2C are similarly associated with poor prognosis. Analysis of TMAs of human PCa patients showed decreased KMT2C expression in bad prognostic high Gleason grade PCa tumour samples. Conclusion Our findings indicate that loss of Kmt2c methyltransferase activity accelerates PCa tumorigenesis in the PtenKmt2cPE-/- mouse model as well as in human patient samples. We therefore propose Kmt2c as a tumour suppressor in prostate cancer.

Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling. Mesenchymal stem cells (MSCs) expressing EF showed high self-renewal capacity and maintained an undifferentiated state despite high apoptosis. Blocking apoptosis through enforced BCL2 family member expression in MSCs promoted efficient and rapid sarcoma formation when transplanted to immunocompromised mice. Mechanistically, high BCL2 family member and CDK4, but low P53 and INK4A protein expression synergized in Ewing-like sarcoma development. Functionally, knockdown of Mcl1 or Cdk4 or their combined pharmacologic inhibition resulted in growth arrest and apoptosis in both established human ES cell lines and EF-transformed mouse MSCs. Combinatorial targeting of survival and cell cycle progression pathways could counteract this aggressive childhood cancer.

Prostate cancer is one of the most prevalent forms of cancer in men worldwide. It remains a clinical challenge to identify lethal metastatic prostate cancers, which escape standard therapeutic intervention. Aberrant interleukin-6 (IL-6) / signal transducer and activator of transcription-3 (STAT3) signalling and loss of p53 occur during prostate cancer progression to metastatic disease. The abnormality of the IL-6/STAT3/p53 axis is frequently accompanied by other genetic alterations; however, its potential role as an important mediator of oncogenic reprogramming, invasion and metastatic transformation remains unknown. The failure of anti-IL-6 treatments is still unexplained and may be due to an incomplete understanding of the mechanism of the in vivo role of IL-6/STAT3 in prostate cancer. The identification of the alternative reading frame protein (ARF) / murine double minute protein (MDM2) / p53 tumour suppressor pathway potentially involving the IL-6/STAT3 axis as a restricting factor in prostate cancer deficient in the tumour suppressor phosphatase and tensin homologue (PTEN) opened new avenues to currently available therapies. This review summarises the current knowledge on the role of crucial pathways driving prostate cancer progression as well as metastatic disease and discusses the potential use of novel specific target molecules and how it can be exploited to avoid overtreatment and increase quality of life.

Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14(ARF) expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.

Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mesenchymal Prx1-directed conditional EF expression in mice to study bone development and to establish a reliable sarcoma model. EF expression arrested early chondrocyte and osteoblast differentiation due to changed signaling pathways such as hedgehog, WNT or growth factor signaling. Mesenchymal stem cells (MSCs) expressing EF showed high self-renewal capacity and maintained an undifferentiated state despite high apoptosis. Blocking apoptosis through enforced BCL2 family member expression in MSCs promoted efficient and rapid sarcoma formation when transplanted to immunocompromised mice. Mechanistically, high BCL2 family member and CDK4, but low P53 and INK4A protein expression synergized in Ewing-like sarcoma development. Functionally, knockdown of Mcl1 or Cdk4 or their combined pharmacologic inhibition resulted in growth arrest and apoptosis in both established human ES cell lines and EF-transformed mouse MSCs. Combinatorial targeting of survival and cell cycle progression pathways could counteract this aggressive childhood cancer.

Interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling is considered to have important oncogenic functions in prostate cancer (PCa). However, a recent study highlighted the central role of IL-6/STAT3 signaling in regulation of the ARF–MDM2–p53 senescence axis. This reversal of the postulated oncogenic properties of IL-6/STAT3 signaling in PCa has important therapeutic implications.

Ewing Sarcoma is a malignant bone tumor in children and young adults. Upon current multimodal therapy only ∼60% of patients are long term survivors. Due to the rarity of the disease, however, only few novel agents can be tested in clinical trials. An animal model closely recapitulating the human disease would be highly needed to more rapidly explore new therapies. Ewing sarcoma is driven by the EWS/FLI1 (EF) chimeric oncogene, an aberrant Ets transcription factor that is toxic to many cell types, but tolerated by mesenchymal stem cells (MSC). Ewing sarcoma is postulated to develop from mesenchymal progenitor cells (MPC), but transgenic approaches tolerating EF expression lack behind. EF expression was shown to induce a differentiation block in MSC but does not drive full transformation. Thus, it was hypothesized that cooperating mutations are required for sarcomagenesis. We challenged this concept in a conditional mouse model in which EWS/FLI1 is activated early during endochondral bone formation by a Prx1-driven Cre recombinase (EFPrx1). EFPrx1 mice follows Mendelian ratio, but newborns suffocated due to a malformed rib cage. Bone formation was blocked at an early chondrocytic stage. EFPrx1 mice lacked limb bones, had reduced calvaria, craniofacial abnormalities and polydactyly. We found that EF expression blocked differentiation of MSC at the pre-hypertrophic chondrocyte stage due to blocked TGF-β and enhanced Hedgehog signaling (down regulated tgfβrI/II, smad1/5, dlx5 and upregulated gli1/2 and caspase 3 mRNA expression). Moreover, EF expression blocked sox9, runx2 and osterix expression. These genes are important for bone differentian. We established MSC-like cells (MSCL) from EFPrx1 mice that self-renewed, but full transformation was absent. We ought to test if the timing of EF induction plays a role, therefor we tested many time points later that the time point described before and we found that when Prx1Cre expression and consequently EWS/FLI1 induction was delayed to a time point after birth using a tamoxifen inducible system, a significant fraction of mice developed solid tumors up to 4 months after Tamoxifen induction. The histo-pathology of the tumors resembled PAS and VIMENTIN positive small round cell tumors, and genetically an EWS/FLI1 signature was seen similar to a patient-derived Ewing sarcoma gene expression pattern. These data suggest that EWS/FLI1 can drive oncogenesis without the need for additional genetic aberrations. We propose that this transgenic mouse model could resemble a faithful model for a solid EWS/FLI1 induced tumor phenocopying human Ewing sarcoma. Citation Format: Tahereh Javaheri, Barbara Sax, Harini Nivarthi, Eleni Tomazou, Mario Mikula, Jan Pencik, Zahra Kazemi, Maximilian Kauer, Marc Wiedner, Jan Tuckermann, Michaela Schlederer, Lukas Kenner, Reinhold Erben, Malkolm Logan, Christine Hartmann, Heinrich Kovar, Richard Moriggl. A mouse model for small round cell tumors induced by the Ewing sarcoma oncogene EWS/FLI1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 61. doi:10.1158/1538-7445.AM2014-61

In the past decades, studies of the Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling have uncovered highly conserved programs linking cytokine signaling to the regulation of essential cellular mechanisms such as proliferation, invasion, survival, inflammation and immunity. Inhibitors of the JAK/STAT pathway are used for treatment of autoimmune diseases, such as rheumatoid arthritis or psoriasis. Aberrant JAK/STAT signaling has been identified to contribute to cancer progression and metastatic development. Targeting of JAK/STAT pathway is currently one of the most promising therapeutic strategies in prostate cancer (PCa), hematopoietic malignancies and sarcomas. Notably, newly identified regulators of JAK/STAT signaling, the non-coding RNAs transcripts and their role as important targets and potential clinical biomarkers are highlighted in this review. In addition to the established role of the JAK/STAT signaling pathway in traditional cytokine signaling the non-coding RNAs add yet another layer of hidden regulation and function. Understanding the crosstalk of non-coding RNA with JAK/STAT signaling in cancer is of critical importance and may result in better patient stratification not only in terms of prognosis but also in the context of therapy.

Simple Summary Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers—NDUFS1 and ATP5O—for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. Abstract 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.