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Prostate cancer is the most common malignancy in men in developed countries. In previous study, we identified HNF1B (Hepatocyte Nuclear Factor 1ß) as a downstream effector of Enhancer of zeste homolog 2 (EZH2). HNF1B suppresses EZH2-mediated migration of two prostate cancer cell lines via represses the EMT process by inhibiting SLUG expression. Besides, HNF1B expression inhibits cell proliferation through unknown mechanisms. Here, we demonstrated that HNF1B inhibited the proliferation rate of prostate cancer cells. Overexpression of HNF1B in prostate cancer cells led to the arrest of G1 cell cycle and decreased Cyclin D1 expression. In addition, we re-explored data from ChIP-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq), and demonstrated that HNF1B repressed Cyclin D1 via direct suppression of SMAD6 expression. We also identified CDKN2A as a HNF1B-interacting protein that would contribute to HNF1B-mediated repression of SMAD6 expression. In summary, we provide the novel mechanisms and evidence in support HNF1B as a tumour suppressor gene for prostate cancer.
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Regulação Neoplásica da Expressão Gênica , Fator 1-beta Nuclear de Hepatócito/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteína Smad6/genética , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/patologia , Ligação Proteica , Proteína Smad6/metabolismoRESUMO
BACKGROUND: Prostate cancer (Pca) remains one of the leading adult malignancies. PTEN (Phosphatase and Tensin Homolog) mutant is the top common mutated genes in prostate cancer, which makes it a promising biomarker in future individualized treatment. METHODS: We obtained gene expression data of prostate cancer from TCGA (The Cancer Genome Atlas) database for analysis. We analyzed the DEGs (differentially expressed genes), and used online tools or software to analyze Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection. RESULTS: Latest TCGA data showed PTEN mutation in about 22% patients. 1736 DEGs in total were identified. Results of gene functional enrichment analyses showed that muscle contraction, negative regulation of growth and multiple metabolic progression were significantly enriched. GNG13, ACTN2, POTEE, ACTA1, MYH6, MYH3, MYH7, MYL1, TNNC1 and TNNC2 were the top ten hub genes. Patients with PTEN mutation showed relatively decreased mRNA expression level of PTEN. Survival analysis indicated the risk of disease recurrence in patients with PTEN mutation. CONCLUSIONS: Our findings suggested that PTEN mutation in prostate cancer may induce changes in a variety of genes and pathways and affect disease progression, suggesting the significance of PTEN mutation in individualized treatment of prostate cancer.
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Biologia Computacional , Mutação , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , PTEN Fosfo-Hidrolase/metabolismo , Medicina de Precisão , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Mapas de Interação de Proteínas , Análise de Sequência de RNARESUMO
BACKGROUND: To evaluate the prognostic value of Lymphovascular Invasion (LVI) in patients with squamous cell carcinoma of the penis (SCCP) following surgery. PATIENTS AND METHODS: This retrospective study analyzed the data of 891 eligible patients with SCCP who were diagnosed between 2010 and 2014, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized by LVI, age, grade, T stage, lymph nodes status, distant metastasis, regional lymph nodes removed, and surgery. Overall survival (OS) and penile carcinoma-specific survival (PCSS) were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The presence of LVI was significantly associated with increased risk of advanced T stage, high grade, lymph node metastasis, and distant metastasis (P < 0.001 for all). In Kaplan-Meier analyses, patients with the presence of LVI had significantly lower OS and PCSS than those with the absence of LVI (P < 0.001 for both,). The presence of LVI was also significantly associated with poorer OS and worse PCSS in patients with Tx + Ta + T1 stage (P = 0.007, P < 0.001), N0 stage (P < 0.001, P = 0.040), grade 1 (P = 0.001, P < 0.001), grade 2 (P = 0.001, P = 0.014), no distant metastasis (P < 0.001 for both), no regional lymph nodes removed (P < 0.001 for both), Non-radical surgery (P < 0.001 for both) and radical surgery(P = 0.037, P = 0.002). In multivariate analyses, the presence of LVI in patients with SCCP following surgery was found to be a significant independent predictor of decreased OS (hazard ratio 1.403, P = 0.039). CONCLUSIONS: The LVI status might be a crucial prognostic indicator for overall survival in patients with SCCP.
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Carcinoma de Células Escamosas/cirurgia , Metástase Linfática/patologia , Neoplasias Penianas/cirurgia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Prognóstico , Estudos Retrospectivos , Programa de SEERRESUMO
Immature dendritic cells (iDCs) have been shown to be able to induce peripheral T-cell tolerance through distinct pathways. Here, we investigated the tolerogenic property of recipient iDCs whose maturation was arrested by a dominant negative mutant of inhibitor of nuclear factor kappa-B kinase 2 (dnIKK2) gene. We found that dnIKK2-iDCs presented a typical semi-mature morphology and expressed lower levels of CD80 and CD86, slightly higher MHC-II than untransfected iDCs. The expression of these molecules had no significant change even dnIKK2-iDCs were pulsed by donor antigen. In primary mixed leukocyte reaction (MLR), dnIKK2-iDCs exhibited impaired ability to stimulate allogeneic T-cells, but induced CD4(+)CD25(-) T-cell formation. In co-culture MLR, these CD4(+)CD25(-) T-cells suppressed T-cell alloreaction in an antigen-specific manner. Besides, CD4(+)CD25(-) T-cells inhibited IL-2 and IFN-γ release, whereas promoted IL-10 and TGF-ß secretion. These data suggested recipient dnIKK2-iDCs could maintain peripheral tolerance through down-regulating costimulatory molecule expressions and inducing CD4(+)CD25(-) T-cell formation.
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Células Dendríticas/imunologia , Quinase I-kappa B/genética , Linfócitos T/imunologia , Animais , Diferenciação Celular , Citocinas/biossíntese , Células Dendríticas/citologia , Quinase I-kappa B/imunologia , Tolerância Imunológica , Isoantígenos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Masculino , Mutação , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Ratos Wistar , Linfócitos T Reguladores/imunologia , TransfecçãoRESUMO
Wilms tumor (WT) is the most common childhood malignant kidney tumor. The aim of the present study was to determine the impact of primary tumor size on the survival of patients with WT. The data of 1,523 patients diagnosed with WT between 2000 and 2017 were retrieved from the Surveillance, Epidemiology, and End Results database. Receiver operating characteristic curves were plotted to determine the optimal cut-off value of primary tumor size. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method and the Cox proportional hazards regression model. The optimal cut-off value for primary tumor size was found to be 11.15 cm. No significant difference in the distribution of tumor size was detected between male and female patients. However, lymph node metastasis and distant metastasis were significantly more frequent in patients whose tumor was ≥11.15 cm in size compared with those with smaller tumors. In addition, patients with larger tumors exhibited significantly worse OS and CSS rates compared with those with smaller tumors. Furthermore, primary tumor size was identified as an independent prognostic factor for OS and CSS in the multivariate analyses. In summary, the present study indicates that primary tumor size is an independent prognostic factor for patients with WT, and tumors ≥11.15 cm are associated with worse OS and CSS.
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Prostate cancer is a major contributor to male mortality worldwide. In this study, we revealed that Ankyrin Repeat and SOCS Box Containing 1 (ASB1) expression was significantly decreased in prostate cancer tissues, correlating strongly with poor patient prognosis. Notably, the group with low ASB1 expression exhibited an increased proportion of M2 macrophages and showed resistance to immune checkpoint inhibitors and cisplatin, but remained sensitive to androgen-receptor-targeting drug bicalutamide. Silencing ASB1 enhanced prostate cancer cell proliferation, clonogenicity, and migration, whereas its overexpression exerted the opposite effects. Through quantitative mass spectrometry interactome analysis, we identified 37 novel proteins interacting with ASB1, including CHCHD3. Subsequent experiments including co-immunoprecipitation, cycloheximide treatment, and ubiquitination assays, revealed that ASB1 interacts with CHCHD3, promoting its degradation via K48-linked ubiquitination. Cell rescue experiments further demonstrated that ASB1 inhibits prostate cancer cell through the CHCHD3/reactive oxygen species (ROS) pathway. Taken together, our study indicated that ASB1 functions as a tumor suppressor by inhibiting CHCHD3/ROS signaling, thereby playing a vital part in prevention of prostate cancer proliferation, clonogenicity, and migration.
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Background: To determine the association between tumor location and both clinicopathological characteristics and the survival of patients with M0 squamous cell carcinoma of the penis (SCCP). Methods: Data of 455 patients diagnosed with M0 SCCP between 1975 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the United States National Cancer Institute. The effects of tumor location on overall survival (OS) and penile carcinoma-specific survival (PCSS) were analyzed using the Kaplan-Meier method. The Cox proportional hazards regression model was used to determine the impact of tumor location on PCSS. Results: SCCP was more likely to occur in the prepuce or glans (90%). Although no significant difference was observed between the OS of patients with M0 SCCP in the prepuce or glans and those with M0 SCCP in the body of the penis (p = 0.307), the former had better PCSS (p = 0.024). Moreover, M0 SCCP in the prepuce or glans was also significantly associated with better PCSS in patients with advanced age (age ≥ 60 years, p = 0.011), other ethnicities (p = 0.003), T2-T4 stage (p = 0.036), larger tumors (≥3 cm, p = 0.001), no regional lymph nodes removed (p = 0.044), and radical surgery (p = 0.027). Multivariate analysis confirmed that tumor location is an independent prognostic factor for patients with M0 SCCP [hazard ratio (HR) 1.881, p = 0.026]. Conclusions: Tumor location is an independent prognostic factor for patients with M0 SCCP, and tumors in the prepuce or glans portend better PCSS.
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Prostate cancer (PCa) is the most common malignancy in men in developed countries. Prostate-specific antigen (PSA) remains the most widely used serum marker for prostate cancer. Here, we reported that the expression of phosphoglucomutase-like protein 5 (PGM5) is significantly lower in prostate cancer tissue. The low expression of PGM5 and its related gene signature were found to be linked to poor clinical outcome and high Gleason score. In vitro assays showed that overexpression of PGM5 significantly repressed proliferation and migration of prostate cancer cells. GO and pathway analyses showed the enrichment of genes in regulation of cell growth and migration, and pathways related in cancer. Our additional results showed that the downregulation of PGM5 is closely related to DNA methylation. Taken together, our findings provide the first evidence that PGM5 expression is associated with prostate cancer progression. These results also highlight a preclinical rationale that PGM5 represents a prognostic marker and a promising target for new therapeutic strategies in prostate cancer.
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BACKGROUND: To evaluate the association of primary tumor size with clinicopathologic characteristics and survival of patients with squamous cell carcinoma of the penis (SCCP). METHODS: This study analyzed the data of 1001 patients with SCCP, obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. The Kaplan-Meier method and the Cox proportional hazards regression model were used to analyze the effects of primary tumor size on overall survival (OS) and penile carcinoma-specific survival (PCSS). RESULTS: Advanced T stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P = 0.001) were more frequently associated with SCCP patients with tumor size ≥ 3 cm than those with tumor size < 3 cm. In Kaplan-Meier analyses, the patients with large tumors (≥ 3 cm) exhibited an inferior OS and PCSS than those with small tumors (< 3 cm). Moreover, tumor size was identified to be an independent prognostic factor for OS [hazard ratio (HR) 1.665, P < 0.001] and PCSS (HR 2.076, P = 0.003) of patients with SCCP in multivariate analyses. CONCLUSIONS: Large tumor size is associated with adverse clinicopathological characteristics of patients with SCCP. Besides, tumor size represents an independent prognostic factor for OS and PCSS. Therefore, clinical assessment of tumor size as a crucial prognostic factor might be highly beneficial for early intervention in patients with SCCP.
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Background: To evaluate impact of marital status on survival of patients with upper urinary tract urothelial carcinoma (UTUC). Methods: Data of patients diagnosed with UTUC from 2010 to 2015 were identified and retrieved from the Surveillance, Epidemiology, and End Results database. The impact of marital status on overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier survival curve method and compared with the log-rank test. Multivariate survival analysis of OS and CSS was conducted using the Cox proportional hazards regression model. Results: A total of 4520 eligible patients with UTUC were included in this study. The 5-year OS rates of married patients, never-married patients, and separated, divorced, or widowed (SDW) patients were 47.3%, 43.7%, and 39.2%, respectively (P < 0.001), and the corresponding 5-year CSS rates were 57.7%, 55.2%, and 51.5%, respectively (P = 0.005). In multivariate analyses, marital status was an independent prognostic factor for OS (P < 0.001) and CSS (P = 0.002) of patients with UTUC. Compared to married patients, never married (hazard ratio [HR], 1.187; 95% confidence interval [CI], 1.016-1.386 for OS; HR, 1.102; 95% CI, 0.877-1.385 for CSS) and SDW (HR, 1.205; 95% CI, 1.094-1.327 for OS; HR, 1.309; 95% CI, 1.131-1.514 for CSS) patients showed poor OS and unfavorable CSS. Conclusions: Marital status was an independent prognostic factor for OS and CSS in patients with UTUC. Married patients with UTUC experienced longer OS and a more favorable CSS than their never married and SDW counterparts.
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Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Estado Civil , Prognóstico , Estudos Retrospectivos , Neoplasias Ureterais/epidemiologiaRESUMO
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage of prostate cancer and the main cause of morbidity and mortality, which is also a potential target for immunotherapy. METHOD: In this study, using the Approximate Relative Subset of RNA Transcripts (CIBERSORT) online method, we analysed the immune cell abundance ratio of each sample in the mCRPC dataset. The EdgeR (an R package) was used to classify differentially expressed genes (DEGs). Using the Database for annotation, visualisation and interactive exploration (DAVID) online method, we performed functional enrichment analyses. STRING online database and Cytoscape tools have been used to analyse protein-protein interaction (PPI) and classify hub genes. RESULTS: The profiles of immune infiltration in mCRPC showed that Macrophages M2, Macrophages M0, T cells CD4 memory resting, T cells CD8 and Plasma cells were the main infiltration cell types in mCRPC samples. Macrophage M0 and T cell CD4 memory resting abundance ratios were correlated with clinical outcomes. We identified 1102 differentially expressed genes (DEGs) associated with the above two immune cells to further explore the underlying mechanisms. Enrichment analysis found that DEGs were substantially enriched in immune response, cell metastasis, and metabolism related categories. We identified 20 hub genes by the protein-protein interaction network analysis. Further analysis showed that three critical hub genes, CCR5, COL1A1 and CXCR3, were significantly associated with prostate cancer prognosis. CONCLUSION: Our findings revealed the pattern of immune cell infiltration in mCRPC, and identified the types and genes of immune cells correlated with clinical outcomes. A new theoretical basis for immunotherapy may be given by our results.
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Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Micrometástase de Neoplasia , PrognósticoRESUMO
CONTEXT: Bladder cancer is one of the most common malignancies worldwide. Some studies noted sex differences in the prognosis of bladder cancer, but results are inconsistent. SUBJECTS AND METHODS: In this study, we assessed whether women with bladder cancer exhibit a worse prognosis, after adjustment for disease stage, age, and body mass index (BMI), using clinical data from The Cancer Genome Atlas. We used a Student's t-test to compare age and BMI in groups with different sexes. STATISTICAL ANALYSIS USED: The Kaplan-Meier method with log-rank test was used to determine clinical prognosis. RESULTS: The BMI (30.15 vs. 26.68, P = 0.0035) and age (67.54 years vs. 66.01 years, P = 0.045) of female patients with muscle-invasive bladder cancer (MIBC) were higher than those of male patients. The overall survival (OS) prognosis of female patients was worse than that of male patients. After grouping by disease characteristics, the disease-free survival (DFS) and OS prognoses of female patients under 60 years of age were worse than those of male patients. In the group with BMI >24, the OS prognosis of female patients was worse than that of male patients, but no difference was found in DFS prognosis. In the group with BMI ≤24, the DFS prognosis of female patients was worse than that of male patients, but no difference was found in OS prognosis. Compared to males, female patients with Stage III disease demonstrated a worse DFS prognosis and poorer OS prognosis, women with stage T3 demonstrated a worse DFS prognosis, and women with stage N0 demonstrated a poorer OS prognosis. No difference was found in prognosis between male and female patients in all other groups. CONCLUSIONS: In patients with MIBC, women tended to exhibit a worse prognosis than men. More specifically, we found a correlation between prognosis and sex after grouping patients by BMI.
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Cistectomia/mortalidade , Neoplasias Musculares/mortalidade , Neoplasias da Bexiga Urinária/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Invasividade Neoplásica , Prognóstico , Fatores Sexuais , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Prostate cancer is still one of the most common malignancies in men all around the world. The mechanism of how prostate cancer initiates and develops is still not clear. Here in this study, we show that tumor suppressor ZBTB38 could suppress the migration and proliferation of prostate cancer cells. We find lower ZBTB38 expression in prostate cancer tissues, which also strongly predicts a poorer prognosis of prostate cancer. ZBTB38 binds DKK1 (Dickkopf WNT signaling pathway inhibitor 1) locus and promotes DKK1 expression in prostate cancer cell lines. Consistently, reduction of DKK1 expression significantly restores ZBTB38-mediated suppression of migration and proliferation of prostate cancer cell lines. Mechanistically, we find that ZBTB38 primarily binds the promoters of target genes, and differentially regulates the expression of 1818 genes. We also identify PRKDC (protein kinase, DNA-activated, catalytic subunit) as a ZBTB38-interacting protein that could repress the function of ZBTB38 in suppressing migration and proliferation of prostate cancer cells. Taken together, our results indicate that ZBTB38 could repress cell migration and proliferation in prostate cancer via promoting DKK1 expression, and also provide evidence supporting ZBTB38 as a potential prognosis marker for prostate cancer.
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Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias da Próstata/genética , Proteínas Repressoras/metabolismo , Animais , Movimento Celular , Proliferação de Células , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/patologia , TransfecçãoRESUMO
OBJECTIVE: To study the expressions of interleukin-15 (IL-15), osteopontin (OPN), granzyme B (GraB) and perforin (PFP) mRNA in early stage of acute rejection (AR) of renal allograft in rats. METHODS: The rat renal transplantation model was established. Male Brown Norway and Lewis rats were used as donors and recipients. Four groups were designated: CsA group (BN-->LEW, n = 10, recipients were treated with CsA i.p.); AB group (BN-->LEW, n = 10, recipients were treated with anti-IL-15 neutralizing antibody i.p.); AR group (BN-->LEW, n = 10, recipients were treated with normal saline i.p.) and control group (LEW-->LEW, n = 6, recipients were treated with normal saline i.p.). The blood samples of recipients were drawn at Days 1, 3, 5 and 7 post-transplantation. The serum expressions of IL-15, OPN, PFP and GraB mRNA of recipients were detected by real-time PCR. Allograft tissues were analyzed by pathological assays. RESULTS: In comparison with other groups, the expressions of OPN, IL-15, PFP and GraB mRNA in AR group were gradually up-regulated and peaked at Day 5. The expressions of IL-15 mRNA in CsA and AB groups were 9685 +/- 1440 and 4346 +/- 741 respectively at Day 5 post-operation. It was significantly lower than that in AR group (17 022 +/- 2153, P < 0.01). The expression of IL-15 mRNA in AB group was significantly lower than that in CsA group (P < 0.01). The expressions of OPN mRNA in CsA and AB groups (13 226 +/- 1565 vs 19 112 +/- 2908) were both significantly lower than that in AR group (24 663 +/- 2449, P < 0.01). But the expression of OPN mRNA in AB group was higher than that in CsA group (P < 0.01). At Day 5 post-transplantation, both the expressions of PFP and GraB mRNA in AB and CsA groups was lower than that in AR group (P < 0.01). The pathological results showed that severe AR occurred at Day 7 post-transplantation in AR group and whereas the extent of rejection sign relieved in AB group. CONCLUSION: In early stage of AR of renal allograft in rats, the expressions of OPN, IL-15, PFP and GraB mRNA are up-regulated. Blocking IL-15/IL-15R pathway in early stage of AR can down-regulate the expressions of PFP and GraB mRNA.
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Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Interleucina-15/metabolismo , Transplante de Rim , Osteopontina/metabolismo , Animais , Rejeição de Enxerto/patologia , Granzimas/metabolismo , Masculino , Proteínas Citotóxicas Formadoras de Poros/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante HomólogoRESUMO
In December 2019, a new type of pneumonia caused by SARS-Cov-2 (COVID-19) occurred in Wuhan and has been discovered in many countries around the world. ACE2 (angiotensin-converting enzyme 2) has been shown to be one of the major receptors that mediate the entry of SARS-Cov-2 into human cells. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicated that ACE2 highly expresses in renal tubular cells, Sertoli cells, Leydig cells, and cells in seminiferous ducts in testis. Recombinant SARS-CoV-2 spike protein (RBD) domain and ACE2 of RPTEC/SerC cell-binding assays confirmed that SARS-Cov-2 can bind to ACE2 on the surface of these cells. Our results suggest that ACE2 expression could contribute to kidney and testis infection after COVID-19 infection. Renal function evaluation and special care should be performed during clinical work. Clinicians should also pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.
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Prostate cancer is the most common malignancy in men in developed countries. Overexpression of enhancer of zeste homolog 2 (EZH2), the major histone H3 lysine 27 methyltransferase, has been connected to prostate cancer malignancy. However, its downstream genes and pathways have not been well established. Here, we show tumor suppressor Hepatocyte Nuclear Factor 1ß (HNF1B) as a direct downstream target of EZH2. EZH2 binds HNF1B locus and suppresses HNF1B expression in prostate cancer cell lines, which is further supported by the reverse correlation between EZH2 and HNF1B expression in clinical samples. Consistently, restored HNF1B expression significantly suppresses EZH2-mediated overgrowth and EMT processes, including migration and invasion of prostate cancer cell lines. Mechanistically, we find that HNF1B primarily binds the promoters of thousands of target genes, and differentially regulates the expression of 876 genes. We also identify RBBP7/RbAP46 as a HNF1B interacting protein which is required for HNF1B-mediated repression of SLUG expression and EMT process. Importantly, we find that higher HNF1B expression strongly predicts better prognosis of prostate cancer, alone or together with lower EZH2 expression. Taken together, we have established a previously underappreciated axis of EZH2-HNF1B-SLUG in prostate cancer, and also provide evidence supporting HNF1B as a potential prognosis marker for metastatic prostate cancer.
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Biomarcadores Tumorais/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator 1-beta Nuclear de Hepatócito/metabolismo , Neoplasias da Próstata/patologia , Fatores de Transcrição da Família Snail/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Fatores de Transcrição da Família Snail/genética , Células Tumorais CultivadasRESUMO
It is well established that the PTEN (Phosphatase and Tensin Homolog) mutant is a frequently mutated gene found in clear cell renal cell carcinoma (ccRCC), making it a potential biomarker for individualized treatment opinions. Here, in the present study, we designed a method to evaluate the significance of the PTEN mutation in the prognosis and drug selection of ccRCC, determine the potential changing pathways and genes associated with the mechanisms. The most recent TCGA data shows that the PTEN mutation is found in 5% of ccRCC patients. In total, 2,569 genes were identified as DEGs. GO and KEGG analysis suggested that DEGs were significantly enriched in categories associated with cell division and multiple metabolic progressions. The top 10 genes, ranked by degree, were identified as hub genes from the protein-protein interaction network (PPI). What is more, patients with the PTEN mutation were associated with a worsened prognosis of ccRCC. Data from the GDSC database indicated that the selective AKT inhibitor, GSK690693, is a selective inhibitor for ccRCC with the PTEN mutation. Our findings have indicated that multiple genes and pathways may play a crucial role in PTEN mutation ccRCC, offering candidate targets and strategies for PTEN mutation ccRCC individualized treatment.
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RATIONALE: Giant mature retroperitoneal teratoma of the adrenal region is quite rare in adults. In most cases, open adrenalectomy is required to ensure complete resection. We describe a case of bilateral giant primary mature cystic teratoma in the region of both adrenal glands in a 22-year-old female patient. PATIENT CONCERNS: A 22-year-old female patient was admitted to our hospital with no complain after detecting to have 2 giant well circumscribed masses in a routine investigation. DIAGNOSES: She was diagnosed with bilateral giant primary mature retroperitoneal teratoma of the adrenal region. INTERVENTIONS: The patient underwent en bloc excision of the mass through laparoscopic simultaneous resection. OUTCOMES: We carefully separated and retained most of the adrenal tissue on both sides during surgery. Pathology reported mature teratomas. Eleven days after operation, the patient made uneventful recovery and left the hospital without any complication. LESSONS: Preoperative imaging and histologic analysis confirmed mature retroperitoneal teratomas. It is feasible to treat such giant benign tumors by laparoscopic simultaneous resection.
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Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Teratoma/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Feminino , Humanos , Teratoma/diagnóstico por imagem , Teratoma/patologia , Adulto JovemRESUMO
Aim: The TP53 mutant is one of the most common mutant genes in prostate cancer. Materials & methods: The RNA-seq data of prostate cancer was downloaded from TCGA database. Gene set and enrichment analyses were done by online tools. Results:TP53 mutation was found in 18% prostate cancer patients. Enrichment analysis indicated that differentially expressed genes were enriched in GPCR signaling pathways, cell growth and metabolism. The top ten hub genes were identified. Further analysis showed increased risk of recurrence, lower TP53 mRNA level and higher Gleason scores in patients with TP53 mutation. Conclusion: Our results suggest that multiple genes and pathways may play key roles in TP53 mutant prostate cancer, providing candidate targets and strategies for individualized treatment.
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Biologia Computacional/métodos , Neoplasias da Próstata/patologia , Proteína Supressora de Tumor p53/genética , Bases de Dados Genéticas , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação , Mutação de Sentido Incorreto , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Mapas de Interação de Proteínas , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: The tumor protein p53 (TP53) mutant is one of the most frequent mutant genes in bladder cancer. In this study, we assessed the importance of the TP53 mutation in bladder cancer progression and drug selection, and identified potential pathways and core genes associated with the underlying mechanisms. METHODS: Gene expression data used in this study were downloaded from The Cancer Genome Atlas and cBioportal databases. Drug sensitivity data were obtained from the Genomics of Drug Sensitivity in Cancer. We did functional enrichment analysis by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We found the TP53 mutation in 50% of bladder cancer patients. Patients with the TP53 mutation were associated with a lower TP53 mRNA expression level, more advanced tumor stage and higher histologic grade. Three drugs, mitomycin-C, doxorubicin and gemcitabine, were especially more sensitive to bladder cancer with the TP53 mutation. As for the mechanisms, we identified 863 differentially expressed genes (DEGs). Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, chemical carcinogenesis and cancer related pathways. The protein-protein interaction network identified the top 10 hub genes. Our results have suggested the significance of TP53 mutation in disease progression and drug selection in bladder cancer, and identified multiple genes and pathways related in such program, offering novel basis for bladder cancer individualized treatment.