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  • Wiley  (11)
  • Zhang, Li  (11)
  • Zhang, Meng  (11)
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  • Wiley  (11)
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  • 1
    Online Resource
    Online Resource
    Immune response drives outcomes in prostate cancer: implications for immunotherapy
    Wiley ; 2021
    In:  Molecular Oncology Vol. 15, No. 5 ( 2021-05), p. 1358-1375
    Details
    In: Molecular Oncology, Wiley, Vol. 15, No. 5 ( 2021-05), p. 1358-1375
    Abstract: The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real‐world samples from our institute (titled the AHMU‐PC cohort). The non‐negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell‐, B cell‐, NK cell‐, and macrophage‐associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune‐activated and immune‐suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF‐β, TGF‐β1, and C‐ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune‐activated subtype, which was associated with favorable recurrence‐free survival outcomes. In addition, patients in the immune‐activated subtype were predicted to benefit more from anti‐PD‐1/PD‐L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    URL: Article
    DOI: 10.1002/mol2.v15.5
    DOI: 10.1002/1878-0261.12887
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2322586-5
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  • 2
    Online Resource
    Online Resource
    4‐Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis
    Wiley ; 2021
    In:  The Prostate Vol. 81, No. 14 ( 2021-10), p. 1078-1090
    Details
    In: The Prostate, Wiley, Vol. 81, No. 14 ( 2021-10), p. 1078-1090
    Abstract: Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis. Materials and Methods First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4‐methylumbelliferone (4‐MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co‐expression network analysis (WGCNA) to identify co‐expressed gene modules and hub‐gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis. Results HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4‐MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co‐expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4‐MU‐treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4‐MU treatment. Conclusions Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4‐MU suppresses the activity of the cell cycle‐related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v81.14
    DOI: 10.1002/pros.24205
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1494709-2
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  • 3
    Online Resource
    Online Resource
    Activated autophagy restored the impaired frequency and function of regulatory T cells in chronic prostatitis
    Wiley ; 2021
    In:  The Prostate Vol. 81, No. 1 ( 2021-01), p. 29-40
    Details
    In: The Prostate, Wiley, Vol. 81, No. 1 ( 2021-01), p. 29-40
    Abstract: Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is a disease with an unclear pathogenesis. Recent studies have reported that regulatory T (Treg) cells might be involved in the development of CP/CPPS. In this study we aimed to examine the functional role of Treg cells and explore the possible regulatory mechanism of Treg cells in CP/CPPS. Methods An experimental autoimmune prostatitis (EAP) mouse model was constructed; the numbers and functions of Treg cells in the EAP and control groups were tested. Then, cell differentiation experiments were conducted to evaluate the regulatory effect of autophagy on Treg cell differentiation. Furthermore, autologous CD4 + CD25 ‐ cells and CD4 + CD25 + cells from the two groups were magnetically sorted and cocultured to observe differences in cellular inhibitory functions. Finally, in an in vivo experiment, rapamycin was intraperitoneally injected into EAP mice for 4 weeks to observe the therapeutic effects. Results We found that the number and function of Treg cells in the EAP group were diminished compared to those in the control group. Meanwhile, the tolerance of pain in EAP mice had also decreased. Moreover, after using the autophagy activator rapamycin, the expression of the inflammatory cytokines interleukin‐1β was decreased and the pain symptoms were alleviated. A mechanistic study found that autophagy activation promoted the differentiation of Treg and increased the suppressive functions of Treg cells, along with the elevated expression of GATA‐3 and cytotoxic T lymphocyte antigen 4 (CTLA‐4). Furthermore, in vivo administration of the autophagy activator rapamycin had similar effects on recovering the frequency and function of Treg cells as well as the expression of GATA‐3 and CTLA‐4. Conclusion The impaired frequency and function of Treg cells may contribute to the progression of CP/CPPS, and autophagy is a protective mechanism that promotes the differentiation of Treg cells and restores the suppressive functions of Treg cells. Autophagy may be a novel therapeutic option for patients with CP/CPPS.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v81.1
    DOI: 10.1002/pros.24073
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Establishment of a five‐enzalutamide‐resistance‐related‐gene‐based classifier for recurrence‐free survival predicting of prostate cancer
    Wiley ; 2022
    In:  Journal of Cellular and Molecular Medicine Vol. 26, No. 21 ( 2022-11), p. 5379-5390
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 26, No. 21 ( 2022-11), p. 5379-5390
    Abstract: To identify prostate cancer (PCa) patients with a high risk of recurrence is critical before delivering adjuvant treatment. We developed a classifier based on the Enzalutamide treatment resistance‐related genes to assist the currently available staging system in predicting the recurrence‐free survival (RFS) prognosis of PCa patients. We overlapped the DEGs from two datasets to obtain a more convincing Enzalutamide‐resistance‐related‐gene (ERRG) cluster. The five‐ERRG‐based classifier obtained good predictive values in both the training and validation cohorts. The classifier precisely predicted RFS of patients in four cohorts, independent of patient age, pathological tumour stage, Gleason score and PSA levels. The classifier and the clinicopathological factors were combined to construct a nomogram, which had an increased predictive accuracy than that of each variable alone. Besides, we also compared the differences between high‐ and low‐risk subgroups and found their differences were enriched in cancer progression‐related pathways. The five‐ERRG‐based classifier is a practical and reliable predictor, which adds value to the existing staging system for predicting the RFS prognosis of PCa after radical prostatectomy, enabling physicians to make more informed treatment decisions concerning adjuvant therapy.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.v26.21
    DOI: 10.1111/jcmm.17554
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2076114-4
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  • 5
    Online Resource
    Online Resource
    Identification of novel susceptibility factors related to CP/CPPS‐like symptoms: Evidence from a multicenter case‐control study
    Wiley ; 2022
    In:  The Prostate Vol. 82, No. 7 ( 2022-05), p. 772-782
    Details
    In: The Prostate, Wiley, Vol. 82, No. 7 ( 2022-05), p. 772-782
    Abstract: We aimed to systematically identify novel susceptible factors related to the occurrence and development of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)‐like symptoms that were not limited to lifestyles or dietary habits in Chinese population. Methods We recruited participants from three centers (Shanghai [northeast], Hefei [east] , and Lanzhou [northwest]) from August 2020 to June 2021. Demographics, lifestyles, dietary habits, past medical history, and national institutes of health‐chronic prostatitis symptom index (NIH‐CPSI) were collected from the individuals via optimized questionnaires. Logistic regression analysis and multivariate adjustment models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the association between these variables and CP/CPPS‐like symptoms. Results A total of 1851 participants were enrolled in this study (764 cases and 1087 controls). Age distributions differed between groups (median, range: 32, 18–74 vs. 29, 18–70, p   〈  0.001). After adjustment, physicochemical occupational hazards were identified significantly related to CP/CPPS‐like symptom occurrence and development (OR occurrence : 1.389, 95% CI: 1.031–1.870, p   〈  0.001; OR development : 2.222, 95% CI: 1.464–3.372, p   〈  0.001); besides, greater than or equal to four ejaculations per week significantly increased the likelihood of CP/CPPS‐like symptoms compared with one ejaculation per week (OR occurrence : 3.051, 95% CI: 1.598–5.827, p  = 0.001). For these patients, who were easily felt gastrointestinal discomfort caused by spicy food intake, they had a higher incidence to affect with CP/CPPS‐like symptoms (OR occurrence : 2.258, 95% CI: 1.858–2.745, p   〈  0.001). In addition, history of drug allergy and genitourinary infections were identified as independent susceptible factors for the occurrence of CP/CPPS‐like symptoms (OR occurrence : 1.689, 95% CI: 1.007–2.834, p  = 0.047; OR occurrence : 3.442, 95% CI: 2.202–5.382, p   〈  0.001, respectively), while the history of rheumatic immune diseases was found tightly associated with the development of CP/CPPS‐like symptoms (OR development : 2.002, 95% CI: 1.008–4.058, p  = 0.048). Conclusion Infection/inflammatory/immune‐related disorders, novel dietary habits, and lifestyles associated with the susceptibility of CP/CPPS‐like symptoms' occurrence and development are identified. Altering these irregular conditions serves as potential strategies for the treatment of patients with CP/CPPS‐like symptoms.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v82.7
    DOI: 10.1002/pros.24319
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1494709-2
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  • 6
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    Cover Image: Volume 82 Issue 7
    Wiley ; 2022
    In:  The Prostate Vol. 82, No. 7 ( 2022-05)
    Details
    In: The Prostate, Wiley, Vol. 82, No. 7 ( 2022-05)
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v82.7
    DOI: 10.1002/pros.24359
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 7
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    Online Resource
    Single‐cell multi‐omics analysis presents the landscape of peripheral blood T‐cell subsets in human chronic prostatitis/chronic pelvic pain syndrome
    Wiley ; 2020
    In:  Journal of Cellular and Molecular Medicine Vol. 24, No. 23 ( 2020-12), p. 14099-14109
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 23 ( 2020-12), p. 14099-14109
    Abstract: Cumulative evidence suggests that abnormal differentiation of T lymphocytes influences the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Thus, understanding the immune activation landscape of CP/CPPS would be helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10 000+ AbSeq profiles and identified fifteen unique T‐cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) was significantly increased compared with the proportion in the healthy control group (9.38%); cluster 0 was defined as effector T cells based on differentially expressed genes/proteins. Flow cytometry assays confirmed that the proportions of effector T‐cell subpopulations, particularly central memory T cells, T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell populations of patients with CP/CPPS were significantly increased compared with those of healthy controls ( P   〈  0.05), further confirming that aberration of effector T cells possibly leads to or intensifies CP/CPPS. Our results provide novel insights into the underlying mechanisms of CP/CPPS, which will be beneficial for its treatment.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.v24.23
    DOI: 10.1111/jcmm.16021
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2076114-4
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  • 8
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    Online Resource
    Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice
    Wiley ; 2020
    In:  The Prostate Vol. 80, No. 9 ( 2020-06), p. 663-673
    Details
    In: The Prostate, Wiley, Vol. 80, No. 9 ( 2020-06), p. 663-673
    Abstract: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS‐associated depression by using a mouse model of experimental autoimmune prostatitis (EAP). Methods Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression‐like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics‐induced pseudo‐germ‐free mice to investigate the effects on host behaviors and the composition of gut bacteria. Results EAP was successfully established and exhibited depressive‐like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics‐treated pseudo‐germ‐free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo‐germ‐free mice, significantly exaggerated host depression‐like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α‐diversity and β‐diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation. Conclusions Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v80.9
    DOI: 10.1002/pros.23978
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1494709-2
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  • 9
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    Online Resource
    Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1‐dependent inhibition of the NLRP3 inflammasome in an EAP mouse model
    Wiley ; 2021
    In:  The Prostate Vol. 81, No. 15 ( 2021-11), p. 1179-1190
    Details
    In: The Prostate, Wiley, Vol. 81, No. 15 ( 2021-11), p. 1179-1190
    Abstract: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti‐inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). Methods The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin‐eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation‐related cytokines, such as interferon‐γ, interleukin (IL)‐17, and IL‐1β, were detected by enzyme‐linked immunosorbent assay. Then, we explored the anti‐inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome‐related proteins in EAP mice. Results The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. Conclusions The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.
    Type of Medium: Online Resource
    ISSN: 0270-4137 , 1097-0045
    URL: Issue
    URL: Article
    DOI: 10.1002/pros.v81.15
    DOI: 10.1002/pros.24214
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1494709-2
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  • 10
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    Establishment of an age‐ and tumor microenvironment‐related gene signature for survival prediction in prostate cancer
    Wiley ; 2022
    In:  Cancer Medicine Vol. 11, No. 22 ( 2022-11), p. 4374-4388
    Details
    In: Cancer Medicine, Wiley, Vol. 11, No. 22 ( 2022-11), p. 4374-4388
    Abstract: The incidence of prostate cancer (PCa) increases with age, and age and tumor microenvironment (TME) have important roles in the development of PCa, while the underlying mechanisms have not been fully elucidated. Materials and method The Cancer Genome Atlas‐Prostate Adenocarcinoma (TCGA‐PRAD) RNA‐Seq, the Surveillance, Epidemiology, and End Results (SEER‐PRAD), and ESTIMATE data were downloaded, and the clinical information of PRAD patients in our cohort was collected. The associations among age, TME, and PCa were analyzed. The age‐ and TME‐related risk score (ATRS) of each TCGA‐PRAD sample was calculated based on the identified age‐ and TME‐related differentially expressed genes (DEGs), and the correlation of ATRS with immune‐related characteristics of PCa patients was analyzed, and the ATRS‐based overall survival (OS)‐predicting nomogram was also established. Results Age was correlated with OS, PSA level, tumor stage, T stage, N stage, Gleason score, nerve invasion of PCa, and age was positively correlated with stromal, immune, and ESTIMATE scores. The compositions of immune cells of TCGA‐PRAD patients altered with age. Nine age‐ and TME‐related prognostic DEGs were identified, and the ATRS of each TCGA‐PRAD patient was calculated based on the identified nine DEGs. The ATRS was associated with the expression of immune checkpoints and intratumoral cytolytic activity, and the ATRS‐based nomogram performed well in predicting the outcomes of PCa patients. Conclusions Age and TME had crucial roles in PCa, and the ATRS gene signature was associated with the immune‐related characteristics of PCa patients, which showed good performance in predicting OS of PCa patients.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    URL: Article
    DOI: 10.1002/cam4.v11.22
    DOI: 10.1002/cam4.4776
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2659751-2
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