RESUMO
A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune-related gene (IRG)-based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF-related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow-up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG-based signature from the specific module. Risk plot analyses, Kaplan-Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell's concordance index were used to assess the prognostic value and predictive accuracy of the IRG-based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG-based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG-based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low-risk and high-risk groups in PRAD. We identified a novel IRG-based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD.
Assuntos
Adenocarcinoma/genética , Redes Reguladoras de Genes , Antígenos HLA/genética , Neoplasias da Próstata/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Colágeno Tipo IV/genética , Seguimentos , Perfilação da Expressão Gênica , Marcadores Genéticos , Humanos , Imunidade Celular , Imunofenotipagem , Estimativa de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Serina-Treonina Quinases/genética , Curva ROC , Análise de Regressão , Medição de Risco , Falha de Tratamento , Microambiente Tumoral/imunologia , Proteínas Supressoras de Tumor/genéticaRESUMO
After publication of the article [1], the author reported that this article contained some errors.
RESUMO
AT-rich interaction domain 4A (ARID4A) and AT-rich interaction domain 4B (ARID4B), which are both the AT-rich interaction domain (ARID) family, have been reported to be oncogene or tumor suppressor gene in various human malignances, but there is no involvement about their functions in prostate cancer (PCa). Our previous study has reported that microRNA-30d (miR-30d) expression can predicted poor clinical prognosis in PCa, however, the underlying mechanisms of miR-30d have not been fully described. The aim of our study is to investigate the expression relevance between miR-30d and ARID4A or ARID4B, and examine the clinical significance and biological function of ARID4A and AIRD4B in PCa. In this study, both ARID4A and ARID4B were identified as the target genes of miR-30d. In addition, the mRNA expression of miR-30d in PCa tissues were significantly negative correlated with ARID4A (Pearson correlation coefficient = -0.313, P = 0.001) and ARID4B (Pearson correlation coefficient = -0.349, P < 0.001), while there was a positive correlation between ARID4A and ARID4B (Pearson correlation coefficient = 0.865, P < 0.001). Moreover, both ARID4A and ARID4B were significantly downregulated in PCa tissues with high Gleason scores (P = 0.005, P = 0.033), PSA failure (P = 0.012, P = 0.05) and short biochemical recurrent-free survival (P = 0.033, P = 0.031). Furthermore, the knockout expression of ARID4A and ARID4B promoted PCa cell proliferation, migration and invasion in vitro. In conclusion, our results indicated that ARID4A and ARID4B may serve as tumor suppressor in PCa progression, suggesting that they might be the potential therapeutic targets in prostate cancer.
Assuntos
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteína 1 de Ligação ao Retinoblastoma/genética , Proteína 1 de Ligação ao Retinoblastoma/metabolismo , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Estudos de Coortes , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Genes Supressores de Tumor , Humanos , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica , Estatísticas não ParamétricasRESUMO
BACKGROUND: Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa. METHODS: Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined. RESULTS: miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells. CONCLUSIONS: miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.
Assuntos
MicroRNAs/genética , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Fosfatase de Miosina-de-Cadeia-Leve/genética , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Interferência de RNARESUMO
Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.
Assuntos
Apoptose/efeitos dos fármacos , Estrogênios/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Benzodioxóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cães , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Próstata/citologia , Hiperplasia Prostática/metabolismo , Quinolinas/farmacologia , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Relação Estrutura-AtividadeRESUMO
BACKGROUND: The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. However, whether aberrant expression of NEK2 is associated with outcome of prostate cancer (PCa) patients remains to be determined. METHODS: Expression of NEK2 in human PCa cells and primary PCa tissues was assessed by quantitative RT-PCR. Expression of NEK2 in human PCa cells was depleted with siRNA. Effects of the depletion on cell proliferation, survival, and tumorigenicity were assessed both in vitro with cell cultures and in vivo with subcutaneous implantation of xenografts. In silico analyses of the online Taylor dataset were carried out to determine whether the expression level of NEK2 correlated with the clinicopathological characteristics of prostate cancer. RESULTS: Compared with benign human prostatic epithelial cells and tissues, the expression of NEK2 was elevated in human PCa cells and primary PCa tissues. Depleting NEK2 expression inhibited human PCa cell proliferation in vitro and xenograft growth in vivo. Expression level of NEK2 in PCa positively correlated with the Gleason score and pathologic stage of the patient. CONCLUSION: The results suggest that overexpression of NEK2 has the potential to serve as a biomarker for PCa prognosis. Further validation with large sample pool is warrant.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Quinases Relacionadas a NIMA , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Regulação para CimaRESUMO
Background: In our previous research, we developed a 32-gene risk index model that may be utilized as a robust prognostic method for predicting prostate cancer (PCa) recurrence after surgery. Among the 32 genes, the Fifth Ewing Variant (FEV) gene was one of the top downregulated genes in relapsed PCa. However, current understanding of the FEV gene and its involvement in PCa is limited. Methods: FEV mRNA expression was analyzed and correlated to clinical outcomes in PCa patients who underwent prostatectomy at the Massachusetts General Hospital. Specimens from tissue microarray (TMA) including 102 prostate cancer patients were analysis for the expression of FEV. Meanwhile, FEV expression profiles were also assessed in PCa cell lines and in BPH-1 prostate epithelial cells using western blotting and quantitative reverse transcription-PCR (qRT-PCR). Furthermore, we transfected LNCaP and PC-3 cells with either an empty vector or full-length FEV gene and performed in vitro cell functional assays. The part FEV plays in tumor xenograft growth was also assessed in vivo. Results: Of the 191 patients included in this study base on the DASL dataset, 77 (40.3%) and 24 (13.6%), respectively, developed prostate-specific antigen (PSA) relapse and metastasis postradical prostatectomy. Significant FEV downregulation was observed in PCa patients showing PSA failure and metastasis. The protein expression of FEV was significantly negatively correlated with the Gleason score and pathological stage in prostate cancer tissues. Similarly, FEV expression significantly decreased in all PCa cell lines relative to BPH-1 (all P < 0.05). Functional assays revealed that FEV expression markedly inhibited PCa cell growth, migration, and invasion, which in turn significantly repressed the growth of tumor xenografts in vivo. Conclusion: The results of this study suggest an association between downregulated FEV expression and PSA relapse in PCa patients. In addition, FEV may act as a tumor suppressor in PCa.
Assuntos
Proteínas de Ligação a DNA , Hiperplasia Prostática , Neoplasias da Próstata , Fatores de Transcrição , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
Subsequently to the publication of this article, one of the corresponding authors, Dr WeiDe Zhong, has realized that the information presented in the box for correspondence for him was incorrect. Although Dr Zhong is correctly shown as having three affiliation addresses in the paper, the address affiliation listed first on the paper should have been presented as the address for correspondence, not the second one. Therefore, the authors' affiliation information should have appeared as follows (changes are highlighted in bold): Correspondence to: Dr Wei De Zhong, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China. Dr Zhong deeply regrets his oversight in this regard, and apologizes for any inconvenience caused. [the original article was published in Oncology Reports 42: 991-1004, 2019; DOI: 10.3892/or.2019.7231].
RESUMO
Previous researchers have demonstrated that microRNA505 (miR505) is negatively correlated with progression in various malignancies. However, the detailed function and molecular mechanisms of miR505 have yet to be completely elucidated in prostate cancer (PCa). The present study initially identified the potential role of miR505 in PCa using in vitro experiments, and demonstrated that restoration of miR505 inhibited proliferation, invasion and migration, yet induced cell cycle arrest and promoted apoptosis in PCa cells. The present study also demonstrated that the expression of neuronglialrelated cell adhesion molecule (NRCAM) was markedly upregulated in PCa cells when compared with benign prostate epithelium. A luciferase reporter assay demonstrated that miR505 directly targeted NRCAM in PCa cells. In addition, NRCAM stimulation antagonized the inhibitory effects of miR505 on the proliferation, migration, and invasion of PCa cells. Furthermore, lower levels of miR505 and higher levels of NRCAM may serve as a predictor of worse biochemical recurrencefree survival or diseasefree survival in patients with PCa. In conclusion, the present study revealed the inhibitory effects of miR505 on PCa tumorigenesis, which potentially occur by targeting NRCAM. The combined analysis of NRCAM and miR505 may predict disease progression in patients with PCa following radical prostatectomy.
Assuntos
Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/patologia , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Moléculas de Adesão Celular/genética , Proliferação de Células , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Taxa de Sobrevida , Células Tumorais Cultivadas , CicatrizaçãoRESUMO
BACKGROUND: Accumulating studies reported that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) may function as either an oncogene or a tumor suppressor in various human cancers. However, its involvement in prostate cancer (PCa) remains unknown. Therefore, the aim of this study was to investigate the clinical significance of HMGCS2 expression and its functions in PCa. METHODS: Expression levels of HMGCS2 mRNA and protein were detected by quantitative Polymerase Chain Reaction (qPCR), Western blot and immunohistochemistry, respectively. Associations of HMGCS2 expression with various clinicopathological features and patients' prognosis of PCa were statistically evaluated. Roles of HMGCS2 dysregulation in cell proliferation, invasion and migration of PCa cell lines were also determined. RESULTS: HMGCS2 protein expression was significantly reduced in PCa tissues compared to adjacent benign prostate tissues at protein levels (P < 0.05). Clinically, low HMGCS2 mRNA expression was dramatically associated with high Gleason score (GS) and pathological grade, as well as the presence of distant metastasis of PCa patients. In addition, PCa patients with low HMGCS2 mRNA expression more frequently had shorter disease-free survival and biochemical recurrence-free survival (all P < 0.05). HMGCS2 expression was identified as an independent factor to predict both disease-free and biochemical recurrence-free survivals of PCa patients. Moreover, loss-of-function experiments demonstrated that HMGCS2 knockdown-expression promotes cell proliferation, colony formation, invasion and migration of PCa cells in vitro and lower the apoptotic rate of PCa cells in vitro. CONCLUSIONS: Our data indicate that HMGCS2 may be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy and functions as a tumor suppressor in PCa cancer, implying its related pathway potential as a drug candidate in anti-PCa therapy.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Hidroximetilglutaril-CoA Sintase/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Próstata/patologia , Neoplasias da Próstata/diagnósticoRESUMO
Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Macrófagos/imunologia , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Microambiente Tumoral/imunologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Quimiocina CXCL2/imunologia , Humanos , Ativação de Macrófagos , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/imunologia , Células PC-3 , Proteínas Serina-Treonina Quinases/fisiologia , Receptores de Superfície Celular/metabolismo , Células THP-1RESUMO
Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry. The association of SRPK2 expression with various clinicopathological characteristics of PCa patients was subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA) dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation, migration, invasion, cell cycle progression, apoptosis and tumor growth were then respectively investigated using in vitro and in vivo experiments. First, public datasets showed that SRPK2 expression was greater in PCa tissues when compared with non-cancerous tissues. Statistical analysis demonstrated that high expression of SRPK2 was significantly correlated with a higher Gleason Score, advanced pathological stage and the presence of tumor metastasis in the TCGA Dataset (all Pâ¯<â¯0.01). Similar correlations between SRPK2 and a higher Gleason Score or advanced pathological stage were also identified in the TMA (Pâ¯<â¯0.05). Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free time of PCa patients with SRPK2 high expression was shorter than for those with SRPK2 low expression (Pâ¯<â¯0.05). Second, cell function experiments in PCa cell lines revealed that enhanced SRPK2 expression could promote cell proliferation, migration, invasion and cell cycle progression but suppress tumor cell apoptosis in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo. In conclusion, our data demonstrated that SRPK2 may play an important role in the progression and metastasis of PCa, which suggests that it might be a potential therapeutic target for PCa clinical therapy.
Assuntos
Progressão da Doença , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Abnormal spindle microtubule assembly (ASPM) gene was known to be linked with poor clinical prognosis in various tumors. However, the clinical significance of ASPM in prostate cancer (PCa) has not yet been understood. The purpose of this study was to determine the association of ASPM with tumor progression and prognosis in PCa patients. METHODS: The expression of ASPM at protein level in human PCa and non-cancerous prostate tissue was detected by immunohistochemical analysis, which was further validated by using microarray-based dataset (NCBI GEO: GSE21032 and The Cancer Genome Atlas (TCGA) dataset) at mRNA level. Subsequently, the association of ASPM expression with the clinicopathological characteristics of patients with PCa was then statistically analyzed. RESULTS: Immunohistochemistry and dataset analyses revealed that ASPM expression was significantly increased in the PCa tissues with high Gleason score. Additionally, as showed by two datasets, ASPM expression was significantly high expressed in the PCa tissues when compared with the non-cancerous tissues, especially in advanced PCa pathological stage. The upregulation of ASPM mRNA expression in the PCa tissues significantly correlated with the presence of tumor metastasis, shorter overall survival and prostate-specific antigen (PSA) failure. Furthermore, both univariate and multivariate analyses showed that the upregulation of ASPM was a potential predictor of poor biochemical recurrence (BCR)-free survival. CONCLUSIONS: Our data suggest that ASPM may play an important role in the progression of PCa. More importantly, the increased expression of ASPM may potentially predict poor BCR-free survival in patients with PCa.
Assuntos
Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Proteínas do Tecido Nervoso/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Biópsia por Agulha , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Análise de Sobrevida , Regulação para CimaRESUMO
BACKGROUND: Novel molecular markers are important diagnostic tools for the assessment of cancer progression and evaluation of effectiveness of the treatment. SOX9, a key regulator of developmental processes, is overexpressed in various neoplasms, such as prostate, breast, and colorectal cancers. However, the utilization of SOX9 as a biomarker for other urological cancers has not yet been investigated. METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the SOX9 protein expression was quantitated as immunoreactive scores in patients with renal cell carcinoma (RCC), bladder cancer (BCa), and penile cancer (PC). RESULTS: In comparison with normal tissues, SOX9 protein expression was signiï¬cantly upregulated in RCC (p < 0.001) and BCa (p < 0.001), and significantly correlated with the advanced pathological grade (RCC: p = 0.023) and clinical stage (RCC: p = 0.022 and BCa: p = 0.046) of patients. Based on the mRNA level in the TCGA dataset, SOX9 was upregulated in RCC with gender (p = 0.027), advanced pathological grade (p = 0.003) and advanced clinical stage (p = 0.001). Kaplan-Meier survival curves revealed that RCC patients with high SOX9 levels had shorter survival (p < 0.001). Further, high SOX9 expression was an independent prognostic factor for RCC patients (hazard ratio 0.056, 95% confidence interval 0.607-1.184; p < 0.001). CONCLUSION: These findings suggest that SOX9 may play an important role in tumor progression of RCC and BCa and it may be used as a biomarker of this malignancy.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Penianas/patologia , Fatores de Transcrição SOX9/metabolismo , Neoplasias da Bexiga Urinária/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Penianas/metabolismo , Prognóstico , RNA Mensageiro/genética , Fatores de Transcrição SOX9/genética , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/metabolismo , Adulto JovemRESUMO
BACKGROUND: Protein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy. MATERIALS AND METHODS: PRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed. RESULTS: PRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P<0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P<0.001). CONCLUSION: These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.
Assuntos
Proteínas de Ciclo Celular/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Proteínas de Ciclo Celular/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Invasividade NeoplásicaRESUMO
Centromere protein F (CENPF) is a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis. Previous studies have demonstrated that the upregulation of CENPF may be used as a proliferation marker of malignant cell growth in tumors. The overexpression of CENPF has also been reported to be associated with a poor prognosis in human cancers. However, the clinical significance of CENPF in prostate cancer (PCa) has not yet been fully elucidated. Thus, the aim of the present study was to determine the association of CENPF with tumor progression and prognosis in patients with PCa. The expression of CENPF at the protein level in human PCa and non-cancerous prostate tissues was detected by immunohistochemical analysis, which was further validated using a microarray-based dataset (NCBI GEO accession no: GSE21032) at the mRNA level. Subsequently, the association of CENPF expression with the clinicopathological characteristics of the patients with PCa was statistically analyzed. Immunohistochemistry and dataset analysis revealed that CENPF expression was significantly increased in the PCa tissues compared with the non-cancerous prostate tissues [immunoreactivity score (IRS): PCa, 177.98 ± 94.096 vs. benign, 121.30 ± 89.596, P < 0.001; mRNA expression in the dataset: PCa, 5.67 ± 0.47 vs. benign, 5.40 ± 0.11; P < 0.001]. Additionally, as revealed by the dataset, the upregulation of CENPF mRNA expression in the PCa tissues significantly correlated with a higher Gleason score (GS, P = 0.005), an advanced pathological stage (P = 0.008), the presence of metastasis (P < 0.001), a shorter overall survival (P=0.003) and prostate-specific antigen (PSA) failure (P < 0.001). Furthermore, both univariate and multivariate analyses revealed that the upregulation of CENPF was an independent predictor of poor biochemical recurrence (BCR)-free survival (P < 0.001 and P = 0.012, respectively). Our data suggest that the increased expression of CENPF plays an important role in the progression of PCa. More importantly, the increased expression of CENPF may efficiently predict poor BCR-free survival in patients with PCa.