Search Results (13)

Prostate cancer remains one of the most prevalent malignancies among men, and emerging evidence proposed a potential role for periprostatic adipose tissue (PPAT) in tumor progression. However, its relationship with imaging-based risk stratification systems such as PI-RADS remains uncertain. This retrospective observational study aimed to evaluate whether periprostatic and subcutaneous fat thickness are associated with PI-RADS scores or PSA levels in biopsy-naïve patients. We retrospectively reviewed 104 prostate MRI scans performed between January 2020 and January 2024. Fat thickness was measured on axial T2-weighted images, and statistical analyses were conducted using Spearman’s correlation and multiple linear regression. In addition to linear measurements, we also assessed periprostatic fat volume and posterior fat thickness derived from imaging data. No significant correlations were observed between fat thickness (either periprostatic or subcutaneous) and PI-RADS score or PSA values. Similarly, periprostatic fat volume showed only a weak, non-significant correlation with PI-RADS, while posterior fat thickness demonstrated a weak but statistically significant positive association. Additionally, subgroup comparisons between low-risk (PI-RADS < 4) and high-risk (PI-RADS ≥ 4) patients showed no meaningful differences in fat measurements. These findings suggest that simple linear fat thickness measurements may not enhance imaging-based risk assessment in prostate cancer, though regional and volumetric assessments could offer modest added value. Full article

Background: Prostate cancer is a major cause of cancer-related mortality among men, with approximately 15% of newly diagnosed patients having pelvic lymph node metastasis (PLNM). For this reason, PLNM identification before localized PCa treatment would significantly impact treatment planning, clinical judgment, and patient outcome prediction. Radiomics has gained popularity for its ability to predict tumor behavior and prognosis without invasive procedures. Magnetic resonance imaging (MRI) is widely used in radiomic workups, particularly for prostate cancer. This study aims to predict lymph node invasion in prostate cancer patients using clinical information and mp-MRI radiomics features extracted from the suspicious nodule, prostate gland, and periprostatic adipose tissue (PPAT). Methods: A retrospective review of 85 patients who underwent mp-MRI at our radiology department between 2016 and 2022 was conducted. This study included patients who underwent prostatectomy and lymphadenectomy with complete histological examination and previous staging mp-MRI and were divided into two groups based on lymph node status (positive/negative). Data were collected from each patient, including clinical information, radiomics, and semantic data (such as tumor MRI characteristics, histological tumor details, and lymph node status (LNS)). MRI exams were conducted using a 1.5-T system and were used to study the prostate gland. A three-year resident manually segmented the prostate nodule, prostatic gland, and periprostatic tissue using an open-source segmentation program. A random forest (RF) machine learning model was developed and tested using Chat-GPT version 4.0 software. The model’s performance in predicting LNS was assessed using accuracy, precision, recall, F1 score, and area under the curve (AUC) receiver operating characteristic (ROC), with sensitivity and specificity evaluated using DeLong’s test. Results: Random forest demonstrated the best performance in prediction considering features extracted from DWI nodules (67% of accuracy, 0.83 AUC), from T2 fat (78% of accuracy, 0.86 AUC), and from T2 glands (78% of accuracy, 0.97 AUC). The combination of the three sequences in the nodule evaluation was more accurate compared with the single sequences (88%). Combining all the nodule features with gland and PPAT features, an accuracy of 89% with AUC near 1 was obtained. Compared with the analysis of the nodule and the PPAT, the whole-gland evaluation had the best performance (p ≤ 0.05) in predicting LNS when compared with the nodule. Conclusions: Precise nodal staging is essential for PCa patients’ prognosis and therapeutic strategy. When compared with a radiologist’s assessment, radiomics models enhance the diagnostic accuracy of lymph node staging for prostate cancer. Although data are still lacking, deep learning models may be able to further improve on this. Full article

Periprostatic adipose tissue (PPAT) contributes to the pathogenesis of prostate cancer. The purpose of this study was to review and summarize the literature on the role of PPAT in prostate cancer pathogenesis. Moreover, we evaluated the clinical implication of PPAT in patients with prostate cancer. We performed a scoping literature review of PubMed from January 2002 to November 2024. Search terms included “periprostatic adipose tissue”, “adipokines”, and “prostate cancer”. Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included PPAT, adipokines, and their role in prostate cancer biology and clinical features. In total 225 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the pathogenesis of PPAT as a contributor to prostate cancer biology and its aggressiveness. The review also presents new research directions for PPAT as a new target for the treatment of prostate cancer. Based on the current review, it can be stated that PPAT plays an important role in prostate cancer pathogenesis. Moreover, PPAT seems to be a promising target point when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer. Full article

Obesity (OB) is a metabolic disorder characterized by adipose tissue dysfunction that has emerged as a health problem of epidemic proportions in recent decades. OB is associated with multiple comorbidities, including some types of cancers. Specifically, prostate cancer (PCa) has been postulated as one of the tumors that could have a causal relationship with OB. Particularly, a specialized adipose tissue (AT) depot known as periprostatic adipose tissue (PPAT) has gained increasing attention over the last few years as it could be a key player in the pathophysiological interaction between PCa and OB. However, to date, no studies have defined the most appropriate internal reference genes (IRGs) to be used in gene expression studies in this AT depot. In this work, two independent cohorts of PPAT samples (n = 20/n = 48) were used to assess the validity of a battery of 15 literature-selected IRGs using two widely used techniques (reverse transcription quantitative PCR [RT-qPCR] and microfluidic-based qPCR array). For this purpose, ΔCt method, GeNorm (v3.5), BestKeeper (v1.0), NormFinder (v.20.0), and RefFinder software were employed to assess the overall trends of our analyses. LRP10, PGK1, and RPLP0 were identified as the best IRGs to be used for gene expression studies in human PPATs, specifically when considering PCa and OB conditions. Full article

Background: The aim of this study was to test the association between periprostatic adipose tissue (PPAT)—apparent diffusion coefficient (ADC) value recorded at multiparametric magnetic resonance imaging (mpMRI) and determinants of prostate cancer (PCa) aggressiveness in the preoperative setting. Methods: Data from 219 consecutive patients undergoing prostate biopsy (PBx) for suspicion of PCa, between January 2020 and June 2022, at our institution were retrospectively evaluated. Only patients who had mpMRI performed before PBx were included. The distribution of demographics and clinical features among PPAT-ADC values up to vs. above the median was studied using both parametric and non-parametric tests, according to variables. Linear and logistic regression models tested the association between PPAT-ADC values and determinants of PCa aggressiveness and the presence of intermediate-high risk PCa, respectively. Results: Of 132 included patients, 76 (58%) had PCa. Median PPAT-ADC was 876 (interquartile range: 654 − 1112) × 10⁻⁶ mm²/s. Patients with PPAT-ADC up to the median had a higher rate of PIRADS (Prostate Imaging—Reporting and Data System) 5 lesions (41% vs. 23%, p = 0.032), a higher percentage of PBx positive cores (25% vs. 6%, p = 0.049) and more frequently harbored ISUP (International Society of Urological Pathology) > 1 PCa (50% vs. 28%, p = 0.048). At univariable linear regression analyses, prostate-specific antigen (PSA), PSA density, PIRADS 5, and percentage of PBx positive cores were associated with lower PPAT-ADC values. PPAT-ADC up to the median was an independent predictor for intermediate-high risk PCa (odds ratio: 3.24, 95%CI: 1.17–9.46, p = 0.026) after adjustment for age and body mass index. Conclusions: Lower PPAT-ADC values may be associated with higher biopsy ISUP grade group PCa and a higher percentage of PBx-positive cores. Higher-level studies are needed to confirm these preliminary results. Full article

Adipose tissue is part of the prostate cancer (PCa) microenvironment not only in the periprostatic area, but also in the most frequent metastatic sites, such as bone marrow and pelvic lymph nodes. The involvement of periprostatic adipose tissue (PPAT) in the aggressiveness of PCa is strongly suggested by numerous studies. Many molecules play a role in the reciprocal interaction between adipocytes and PCa cells, including adipokines, hormones, lipids, and also lipophilic pollutants stored in adipocytes. The crosstalk has consequences not only on cancer cell growth and metastatic potential, but also on adipocytes. Although most of the molecules released by PPAT are likely to promote tumor growth and the migration of cancer cells, others, such as the adipokine adiponectin and the n-6 or n-3 polyunsaturated fatty acids (PUFAs), have been shown to have anti-tumor properties. The effects of PPAT on PCa cells might therefore depend on the balance between the pro- and anti-tumor components of PPAT. In addition, genetic and environmental factors involved in the risk and/or aggressiveness of PCa, including obesity and diet, are able to modulate the interactions between PPAT and cancer cells and their consequences on the growth and the metastatic potential of PCa. Full article

The increased global prevalence of metabolic disorders including obesity, insulin resistance, metabolic syndrome and diabetes is mirrored by an increased incidence of prostate cancer (PCa). Ample evidence suggests that these metabolic disorders, being characterized by adipose tissue (AT) expansion and inflammation, not only present as risk factors for the development of PCa, but also drive its increased aggressiveness, enhanced progression, and metastasis. Despite the emerging molecular mechanisms linking AT dysfunction to the various hallmarks of PCa, thromboinflammatory processes implicated in the crosstalk between these diseases have not been thoroughly investigated. This is of particular importance as both diseases present states of hypercoagulability. Accumulating evidence implicates tissue factor, thrombin, and active factor X as well as other players of the coagulation cascade in the pathophysiological processes driving cancer development and progression. In this regard, it becomes pivotal to elucidate the thromboinflammatory processes occurring in the periprostatic adipose tissue (PPAT), a fundamental microenvironmental niche of the prostate. Here, we highlight key findings linking thromboinflammation and the pleiotropic effects of coagulation factors and their inhibitors in metabolic diseases, PCa, and their crosstalk. We also propose several novel therapeutic targets and therapeutic interventions possibly modulating the interaction between these pathological states. Full article

Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differentiated adipocytes isolated from PPAT taken from PCa patients during radical prostatectomy. Migration was studied by scratch assay. Results: Culture with CM of human PPAT (AdipoCM) promotes migration in two different human androgen-independent (AI) PCa cell lines (DU145 and PC3) and upregulated the expression of CTGF. SB431542, a well-known TGFβ receptor inhibitor, counteracts the increased migration observed in presence of AdipoCM and decreased CTGF expression, suggesting that a paracrine secretion of TGFβ by PPAT affects motility of PCa cells. Conclusions: Collectively, our study showed that factors secreted by PPAT enhanced migration through CTGF upregulation in AI PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and TGFβ/CTGF axis to fight advanced PCa dissemination. Full article

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer. Full article

Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- and adipokines. Together, myokines and adipokines may act in an endocrine-like manner to favor communication between skeletal muscle and WAT, as they may work together to improve whole-body metabolic health. This crosstalk may constitute a potential mechanism by which ET exerts its beneficial role in the prevention and treatment of PCa-related disorders; however, this has not yet been explored. Therefore, we reviewed the current evidence on the effects of skeletal muscle–WAT–tumor crosstalk in PCa, and the potential mediators of this process to provide a better understanding of underlying ET-related mechanisms in cancer. Full article

This study aimed to assess the prognostic value of computed tomography (CT)-attenuation and ¹⁸F-fluorodeoxyglucose (FDG) uptake of periprostatic adipose tissue (PPAT) for predicting disease progression-free survival (DPFS) in patients with prostate cancer. Seventy-seven patients with prostate cancer who underwent staging FDG positron emission tomography (PET)/CT were retrospectively reviewed. CT-attenuation (HU) and FDG uptake (SUV) of PPAT were measured from the PET/CT images. The relationships between these PPAT parameters and clinical factors were assessed, and a Cox proportional hazard regression test was performed to evaluate the prognostic significance of PPAT HU and SUV. PPAT HU and SUV showed significant positive correlations with tumor stage and serum prostate-specific antigen level (PSA) (p < 0.05). Patients with high PPAT HU and SUV had significantly worse DPFS than those with low PPAT HU and SUV (p < 0.05). In multivariate analysis, PPAT SUV was a significant predictor of DPFS after adjusting for tumor stage, serum PSA, and tumor SUV (p = 0.003; hazard ratio, 1.50; 95% confidence interval, 1.15–1.96). CT-attenuation and FDG uptake of PPAT showed significant association with disease progression in patients with prostate cancer. These imaging findings may be evidence of the role of PPAT in prostate cancer progression. Full article

The prostate is surrounded by periprostatic adipose tissue (PPAT), the thickness of which has been associated with more aggressive prostate cancer (PCa). There are limited data regarding the functional characteristics of PPAT, how it compares to subcutaneous adipose tissue (SAT), and whether in a setting of localized PCa, these traits are altered by obesity or disease aggressiveness. PPAT and SAT were collected from 60 men (age: 42–78 years, BMI: 21.3–35.6 kg/m²) undergoing total prostatectomy for PCa. Compared to SAT, adipocytes in PPAT were smaller, had the same basal rates of fatty acid release (lipolysis) yet released less polyunsaturated fatty acid species, and were more sensitive to isoproterenol-stimulated lipolysis. Basal lipolysis of PPAT was increased in men diagnosed with less aggressive PCa (Gleason score (GS) ≤ 3 + 4) compared to men with more aggressive PCa (GS ≥ 4 + 3) but no other measured adipocyte parameters related to PCa aggressiveness. Likewise, there was no difference in PPAT lipid biology between lean and obese men. In conclusion, lipid biological features of PPAT do differ from SAT; however, we did not observe any meaningful difference in ex vivo PPAT biology that is associated with PCa aggressiveness or obesity. As such, our findings do not support a relationship between altered PCa behavior in obese men and the metabolic reprogramming of PPAT. Full article

The composition of periprostatic adipose tissue (PPAT) has been shown to play a role in prostate cancer (PCa) progression. We recently reported an inverse association between PCa aggressiveness and elevated PPAT linoleic acid (LA) and eicosapentaenoic acid (EPA) content. In the present study, we identified a new signaling pathway with a positive feedback loop between the epithelial-to-mesenchymal transition (EMT) transcription factor Zeb1 and the Ca²⁺-activated K⁺ channel SK3, which leads to an amplification of Ca²⁺ entry and cellular migration. Using in vitro experiments and ex vivo cultures of human PCa slices, we demonstrated that LA and EPA exert anticancer effects, by modulating Ca²⁺ entry, which was involved in Zeb1 regulation and cancer cellular migration. This functional approach using human prostate tumors highlights the clinical relevance of our observations, and may allow us to consider the possibility of targeting cancer spread by altering the lipid microenvironment. Full article