Prostate最新文献

Background: Multiple novel protein biomarkers have been shown to be associated with prostate cancer risk using genetic instruments. This study aimed to externally validate the associations of 30 genetically predicted candidate proteins with prostate cancer risk using aptamer-based levels in US Black and White men in the Atherosclerosis Risk in Communities (ARIC) study. Plasma protein levels were previously measured by SomaScan® using the blood collected in 1990-1992.

Methods: Among 4864 eligible participants, we ascertained 667 first primary prostate cancer cases through 2015. Hazard ratios (HRs) of prostate cancer and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression for tertiles of each protein. We adjusted for age, race, and other risk factors.

Results: Of the 30 proteins and considering a nominal p trend < 0.05, two were positively associated with prostate cancer risk-RF1ML (tertile 3 vs. 1: HR = 1.23; 95% CI 1.02-1.48; p trend = 0.037) and TPST1 (1.28, 95% CI 1.06-1.55; p trend = 0.0087); two were inversely associated-ATF6A (HR = 0.80, 95% CI 0.65-0.98; p trend = 0.028) and SPINT2 (HR = 0.74, 95% CI 0.61-0.90; p trend = 0.0025). One protein, KDEL2, which was nonlinearly associated (test-for-linearity: p < 0.01) showed a statistically significant lower risk in the second tertile (HR = 0.79, 95% CI 0.65-0.95). Of these five, four proteins-ATF6A, KDEL2, RF1ML, and TPST1-were consistent in the direction of association with the discovery studies.

Conclusion: This study validated some pre-diagnostic protein biomarkers of the risk of prostate cancer.

Background: Prostate cancer is a complex disease that develops over time and is influenced by several lifestyle factors that also impact gut microbes. Gut dysbiosis is intricately linked to prostate carcinogenesis, but the precise mechanisms remain poorly understood. Mice are crucial for studying the relationships between gut microbes and prostate cancer, but discovering similarities between humans and mice may aid in elucidating new mechanisms.

Methods: We used 16s rRNA sequencing data from stool samples of tumor-bearing prostate-specific conditional Pten-knockout mice, disease-free wildtype mice, and a human cohort suspected of having prostate cancer to conduct taxonomic and metagenomic profiling. Features were associated with prostate cancer status and low risk (a negative biopsy of Gleason grade <2) or high risk (Gleason grade ≥2) in humans.

Results: In both humans and mice, community composition differed between individuals with and without prostate cancer. Odoribacter spp. and Desulfovibrio spp. were taxa associated with prostate cancer in mice and humans. Metabolic pathways associated with cofactor and vitamin synthesis were common in mouse and human prostate cancer, including bacterial synthesis of folate (vitamin B9), ubiquinone (CoQ10), phylloquinone (vitamin K1), menaquinone (vitamin K2), and tocopherol (vitamin E).

Conclusions: Our study provides valuable data that can help bridge the gap between human and mouse microbiomes. Our findings provide evidence to support the notion that certain bacterial-derived metabolites may promote prostate cancer, as well as a preclinical model that can be used to characterize biological mechanisms and develop preventive interventions.

Purpose: To assess the early metabolic response of the primary tumor using Gallium-68 (⁶⁸Ga)-labeled-prostate-specific membrane antigen positron emission tomography (⁶⁸Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients.

Methods: The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed.

Results: The median duration between pre- and Posttreatment ⁶⁸Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without.

Conclusions: Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using ⁶⁸Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

Background: To analyze the expression of interleukin-33 (IL-33), growth-stimulated expression gene 2 (ST2), nuclear factor-kappaB (NF-κB) and immune cell infiltration in prostate cancer, this study aims to provide an experimental basis for the clinical prevention and treatment of prostate cancer.

Methods: The expression of IL-33 in PCa tissues was analyzed using TCGA, TIMER and HPA databases. Using the UALCAN database, the systematic exploration of the relationship between IL-33 and various clinicopathological parameters was conducted. The correlation between IL-33 expression and immune cell infiltration was investigated using TIMER, CIBERSORT and GEPIA databases. To verify these analyses, 22 cases of normal prostate (NP), 76 cases of benign prostatic hyperplasia (BPH), and 100 cases of PCa were recruited. Immunohistochemical staining was performed to examine the expression of IL-33, ST2, NF-κB, and the infiltration of immune cells. Correlations between these factors were then determined.

Results: The expression of IL-33, ST2 and NF-κB was significantly lower in PCa tissues compared with NP (p < 0.05). IL-33 was not associated with age in PCa but showed associations with race, molecular characteristics, lymph node metastatic status, TP53 mutation and tumor grade. Furthermore, IL-33 was associated with immune cell infiltration. Positive correlations were observed between IL-33 and ST2 expressions, as well as between IL-33 and CD68⁺ macrophages in BPH and PCa.

Conclusions: IL-33, ST2 and NF-κB are lowly expressed in PCa tissues, their expression decreases with the increasing malignancy of cancer. IL-33, ST2 and NF-κB are factors associated with PCa immune infiltration. IL-33 has an inhibitory effect on prostate cancer through the IL-33/ST2/NF-κB signalling pathway.

Introduction and objectives: Prostate magnetic resonance imaging (MRI) is used for prostate cancer (PCa) screening and risk stratification and is helpful for surgical planning for patients undergoing holmium laser enucleation of the prostate (HoLEP). There are few studies investigating the correlation between MRI Prostate Imaging-Reporting and Data System (PIRADS) lesion characteristics and HoLEP pathology and outcomes.

Methods: We performed retrospective review of patients who underwent HoLEP between January 2021 and August 2023 by a single surgeon. Preoperative, intraoperative, and postoperative characteristics and outcomes were analyzed for all patients who had a documented preoperative prostate MRI.

Results: There were 334 patients without a pre-existing diagnosis of PCa and with a preoperative prostate MRI, of which 140 (42%) had at least one PIRADS lesion. There was a total of 203 PIRADS lesions: 91 (45%) in the peripheral zone (PZ), 106 (52%) in the transition zone (TZ), and 6 (2%) not specified. Incidental PCa was noted in 44 (13%) patients at time of HoLEP. Presence or location of lesion was not significantly associated with rate or grade of incidental PCa on pathology. Greater number of lesions and lesion size correlated with longer procedure times. Lesion number, size, or grade were not found to correlate with cancer grade or rate of cancer.

Conclusions: Grade, presence, location, size, and number of PIRADS lesions on preoperative prostate MRI for patients with an appropriate prior PCa workup were not significantly associated with incidental PCa or higher PCa grade on HoLEP pathology.