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1.
Zhonghua Nan Ke Xue ; 27(8): 718-724, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34914244

RESUMO

Objective: To investigate the influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4-10 µg/L. METHODS: We reviewed the clinical data on 317 patients with a PSA level of 4-10 µg/L on prostate biopsy performed in The First Affiliated Hospital of Fujian Medical University between May 2012 and May 2019, concerning age, body mass index (BMI), prostate volume, PSA level, FPSA/TPSA ratio, PSA density (PSAD), scores on Prostate Imaging Reporting and Data System version 2 (PI-RADS), prostatic calculi and pathological findings. Using logistic regression analysis and ROC curves, we evaluated the influence of prostatic calculi on the results of prostate biopsy. RESULTS: Multivariate analysis showed that age and the PI-RADS score were independent risk factors of positive prostate biopsy, while the prostate volume, FPSA/TPSA ratio and calculus burden were independent protective factors, and that the PI-RADS score was an independent risk factor of clinically significant PCa, while calculus burden and FPSA/TPSA ratio were independent protective factors. Subgroup analysis of the prostatic calculi revealed that the rates of positive prostate biopsy and clinically significant PCa were higher in the patients with calculi in the peripheral zone than in the other groups, but lower in those with calculi in the central or transitional zone than in the peripheral zone and non-calculus groups. CONCLUSIONS: The rates of positive prostate biopsy and clinically significant PCa are low in prostatic calculus patients with a PSA level of 4-10 µg/L, especially in those with calculi in the central or transitional zone.


Assuntos
Cálculos , Neoplasias da Próstata , Biópsia , Cálculos/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico
2.
Clin Nutr ; 40(12): 5792-5801, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34775222

RESUMO

OBJECTIVE: To investigate the predictors of response to intravesical Bacillus Calmette-Guerin (BCG) immunotherapy for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) patients. MATERIALS AND METHODS: We retrospectively analyzed the clinicopathological data of 184 intermediate and high risk NMIBC cases receiving transurethral resection of bladder tumor (TURBT) and intravesical BCG immunotherapy from December 2014 to April 2021 at our center. All patients were divided into BCG responders and non-responders. Multivariate Logistic regression analysis was performed to identify the independent predictors of response to intravesical BCG immunotherapy. Univariate and multivariate Cox regression analyses were applied to explore the independent prognostic factors of recurrence-free survival (RFS). Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis were also utilized. RESULTS: The RFS of BCG responders was significantly increased compared with BCG non-responders. Multivariate Cox regression analysis demonstrated that low grade, pTa stage, non-CIS, lower relative visceral fat area (rVFA) and lower systemic immune inflammation index (SII) were independent prognostic factors of increased RFS after intravesical BCG immunotherapy. Multivariate Logistic regression analysis demonstrated that pTa stage, low grade, non-CIS, low rVFA, and low SII were independent predictors of response to intravesical BCG immunotherapy. Kaplan-Meier survival analysis indicated that the RFS of patients in low rVFA group or low SII group was significantly increased in comparison with those in high rVFA group or high SII group. ROC curve analysis showed that the area under ROC (AUC) of including SII and rVFA was significantly increased, indicating that the inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency. CONCLUSIONS: Low grade, pTa stage, non-CIS, preoperative lower rVFA and lower SII were vital independent predictors of response to intravesical BCG immunotherapy and were associated with preferable prognosis in NMIBC patients. The inclusion of preoperative SII and rVFA could significantly improve the predictive efficiency.

3.
Pathol Oncol Res ; 27: 1609941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776794

RESUMO

Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa). Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated. Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients. Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

4.
Front Oncol ; 11: 615881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631509

RESUMO

Objective: To explore whether preoperative 18Fluorine-Fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in combination with neutrophil-lymphocyte ratio (NLR) could accurately predict malignant lesions of upper urinary tract (UUT). Methods and Materials: The clinicopathologic data of a total of 252 patients with UUT lesions receiving surgical treatment at our center from January 2012 to November 2019 were retrospectively analyzed. All patients performed routine preoperative hematological examination, urine cytology, computed tomography urography (CTU), and 18F-FDG-PET/CT. Clinicopathologic data between 179 cases with malignancy (Group 1) and 73 cases with benign lesions (Group 2) were compared. Multivariate logistic regression analysis was used to explore the independent predictors of malignant UUT lesions. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability. Results: Among all patients, univariate analysis showed that NLR, hydronephrosis, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis revealed that NLR, CTU indicating malignancy, and PET/CT indicating malignancy were independent predictors of malignant UUT lesions; the area under ROC curve (AUC) of NLR, CTU, PET/CT, combining CTU and NLR, combining PET/CT and NLR, and combining PET/CT and CTU were 0.735, 0.788, 0.857, 0.863, 0.913, and 0.919, respectively, for postoperative pathological malignancy. Among 68 patients undergoing ureteroscopy biopsy, univariate analysis suggested that NLR, positive urine exfoliation cytology, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis demonstrated that positive urine cytology, PET/CT indicating malignancy, and NLR were independent predictors of malignant UUT lesions; the AUC of NLR, ureteroscopy biopsy, and combining PET/CT and NLR were 0.768, 0.853, and 0.839, respectively, for postoperative pathological malignancy. Conclusions: Combining preoperative NLR and PET/CT performed well in differentiating benign from malignant UUT lesions, which could not be identified by traditional imaging or urine cytology. Combining preoperative NLR and PET/CT could be used to reduce unnecessary ureteroscopy biopsy, which might result in tumor cell dissemination and risk of associated complications.

5.
Int J Gen Med ; 14: 6325-6342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629897

RESUMO

Background: This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis. Materials and Methods: The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively. Results: We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P<0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P<0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies. Conclusion: We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.

6.
Front Oncol ; 11: 634075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268107

RESUMO

M2-tumor-associated macrophages (TAMs) work as a promoter in the processes of bone metastases, chemotherapy resistance, and castration resistance in prostate cancer (PCa), but how M2-TAMs affect PCa has not been fully understood. In this study, we analyzed the proportion of tumor-infiltrating immune cells using the CIBERSORT algorithm, based on samples from the Cancer Genome Atlas database. Then we performed weighted gene co-expression network analysis to examine the modules concerning infiltrated M2-TAMs. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was constructed. The International Cancer Genomics Consortium cohort was used as a validation cohort. The red module showed the most correlation with M2-TAMs in PCa. Biological processes and pathways were mainly associated with the immune-related processes, as revealed by functional annotation. Four hub genes were screened: ACSL1, DLGAP5, KIF23 and NCAPG. Further validation showed that the four hub genes had a higher expression level in tumor tissues than that in normal tissues, and they were good prognosis biomarkers for PCa. In conclusion, these findings contribute to understanding the underlying molecular mechanisms of how M2-TAMs affect PCa, and looking for the potential biomarkers and therapeutic targets for PCa patients.

7.
J Inflamm Res ; 14: 3217-3229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285545

RESUMO

Background: Urethral stricture is a clinical challenge for both patients and clinicians. Post-traumatic urethral stricture is associated with formation of scar tissue caused by excessive inflammation. The aim of this study is exploring potential therapeutic strategies for this condition. Methods: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1ß-treated mesenchymal stem cells (Exo-MSCsIL-1ß) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored. Results: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL-1ß significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL-1ß to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL-1ß were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3'UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway. Conclusion: These results support a role for let-7c-containing Exo-MSCsIL-1ß in reducing urethral stricture via inhibition of PAK1-NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.

8.
Cell Death Dis ; 12(4): 302, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753726

RESUMO

Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K-AKT-mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K-AKT-mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K-AKT-mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.


Assuntos
/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Animais , Proliferação de Células/fisiologia , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais
9.
BMC Cancer ; 21(1): 79, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468079

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most frequent malignancies; however, the present prognostic factors was deficient. This study aims to explore whether there is a relationship between tumor volume (TV) and oncological outcomes for localized ccRCC. METHODS: Seven hundred forty-nine localized ccRCC patients underwent surgery in our hospital. TV was outlined and calculated using a three-dimensional conformal radiotherapy planning system. We used receiver operating characteristic (ROC) curves to identified optimal cut-off value. Univariable and multivariable Cox regression models were performed to explore the association between TV and oncological outcomes. Kaplan-Meier method and log-rank test were used to estimate survival probabilities and determine the significance, respectively. Time-dependent ROC curve was utilized to assess the prognostic effect. RESULTS: Log rank test showed that higher Fuhrman grade, advanced pT classification and higher TV were associated with shortened OS, cancer-specific survival (CSS), freedom from metastasis (FFM) and freedom from local recurrence (FFLR). multivariable analysis showed higher Fuhrman grade and higher TV were predictors of adverse OS and CSS. The AUC of TV for FFLR was 0.822. The AUC of TV (0.864) for FFM was higher than that of pT classification (0.818) and Fuhrman grade (0.803). For OS and CSS, the AUC of TV was higher than that of Fuhrman grade (0.832 vs. 0.799; 0.829 vs 0.790). CONCLUSIONS: High TV was an independent predictor of poor CSS, OS, FFLR and FFM of localized ccRCC. Compared with pT classification and Fuhrman grade, TV could be a new and better prognostic factor of oncological outcome of localized ccRCC, which might contribute to tailored follow-up or management strategies.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Rim/patologia , Recidiva Local de Neoplasia/epidemiologia , Nefrectomia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Rim/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Curva ROC , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
10.
J Cancer ; 12(4): 1249-1257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33442423

RESUMO

The diverse tumor cell populations may be the critical roles in relapse and resistance to treatment in prostate cancer patients. This study aimed to identify new marker genes and cell subtypes among castration-resistant prostate cancer (CRPC) cells. We downloaded single-cell RNA seq profiles (GSE67980) from the Gene Expression Omnibus (GEO) database. Principal component (PC) analysis and t-Distributed Stochastic Neighbor Embedding (TSNE) analysis were performed to identify marker genes. CRPC cells were clustered and annotated. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses among marker genes were performed. A total of 1500 genes with larger standardized variance were obtained. The top 20 genes were demonstrated in each identified 20 PCs. PC with P-value < 0.05 was selected, including PC1, PC7, PC8, and PC14. The TSNE analysis classified cells as two clusters. The top 6 genes in cluster 0 included HBB, CCL5, SLITRK4, GZMB, BBIP1, and PF4V1. Plus, the top 6 genes in cluster 1 included MLEC, CCT8, CCT3, EPCAM, TMPRSS2, EIF4G2. The GO analysis revealed that these marker genes were mainly enriched in RNA catabolic process, translational initiation, mitochondrial inner membrane, cytosolic part, ribosome, cell adhesion molecule binding, cadherin binding, and structural constituent of ribosome. The KEGG analysis showed that these marker genes mainly enriched in metabolism associated pathways, including carbon metabolism, cysteine and methionine metabolism, propanoate metabolism, pyruvate metabolism, and citrate cycle pathways. To conclude, our results provide essential insights into the spectrum of cellular heterogeneity within human CRPC cells. These marker genes, GO terms and pathways may be critical in the development and progression of human CRPC.

11.
Asian J Surg ; 44(1): 80-86, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32291131

RESUMO

PURPOSE: To determine the risk factors of intraoperative cyst rupture in partial nephrectomy (PN) for a cystic renal mass (CRM) and their effect on the prognosis of patients. MATERIALS AND METHODS: Patients who underwent partial nephrectomy for CRMs from January 2009 to January 2015 were included. Uni/multivariate Logistic/Cox analysis and Kaplan-Meier analysis were performed. RESULTS: A total of 174 patients were included in this study. There were 27 (15.5%) intraoperative cyst ruptures. The median follow-up time was 60 months. Multivariate logistic analysis showed that the E component (P = 0.018) and N component (P = 0.022) of the R.E.N.A.L. nephrometry score, Bosniak category III (P = 0.044), and surgeon's experience (P = 0.030) were risk factors associated with intraoperative cyst rupture in PN for CRMs. The 5-year recurrence-free survival (RFS), cancer-free survival (CFS) and overall survival (OS) were 92.7%, 90.32% and 94.4%, respectively, in 124 cases of malignant CRM. Kaplan-Meier analysis demonstrated that 5-year RFS and 5-year CFS in patients with cyst rupture was worse than those without cyst rupture (P = 0.006 and 0.003, respectively). Multivariate Cox analysis revealed that intraoperative cyst rupture was independent risk factor for 5-year RFS and 5-year CFS (P = 0.039 and 0.013, respectively). However, there was no significant difference in OS between the two groups (P = 0.275). CONCLUSIONS: The prevalence of intraoperative cyst rupture is relatively high. Higher E and N scores, Bosniak category III, and lacking surgical experience (<20 cases) increase the risk of occurrence of intraoperative cyst rupture.


Assuntos
Complicações Intraoperatórias/etiologia , Doenças Renais Císticas/cirurgia , Nefrectomia/métodos , Ruptura Espontânea/etiologia , Adulto , Idoso , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Estimativa de Kaplan-Meier , Doenças Renais Císticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Ruptura Espontânea/epidemiologia , Taxa de Sobrevida
12.
J Cell Physiol ; 236(1): 706-713, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32617980

RESUMO

Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular cancer microenviroment based on ESTIMATE algorithm-derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high- and low-score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response-regulating cell surface receptor signaling pathway, immune response-activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6-196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Testiculares/metabolismo , Transcriptoma/imunologia , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/imunologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/imunologia , Microambiente Tumoral/imunologia
13.
Genomics ; 113(1 Pt 2): 531-540, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979493

RESUMO

OBJECTIVE: To screen several immune-related long non-coding RNAs (lncRNAs) and construct a prognostic model for papillary renal cell carcinoma (pRCC). METHODS: Transcriptome-sequencing data of pRCC was downloaded and a prognostic model was constructed. Time-dependent receiver operating characteristic (ROC) curve was plotted and the area under curve (AUC) was calculated. We conducted quantitative reverse transcription polymerase chain reaction (RT-PCR) to verify the model. The gene set enrichment analysis (GSEA) was used to show the connection of our model with immune pathways. RESULT: We identified four lncRNAs to constructed the model. The model was significantly associated with the survival time and survival state. The expression-levels of the four lncRNAs were measured and the prognosis of high-risk patients was significantly worse. The two immune-gene sets had an active performance in the high-risk patients. CONCLUSION: We constructed a prognostic model in pRCC which provided more reference for treatment.

14.
Int J Gen Med ; 14: 10003-10013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34984024

RESUMO

Objective: To develop and validate hub genes involving in the development and progression of primary aldosteronism (PA) and adrenal aldosterone-producing adenoma (APA). Materials and Methods: A total of four datasets of gene expression profiles related to APA were downloaded from GEO datasets. GSE60042 and GSE8514 were used to identify DEGs. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network module analysis were conducted. GO and KEGG enrichment analysis was performed. GSE10927 and GSE33371 were used for further external validation. Results: We identified a total of 892 DEGs from GSE60042 and 1167 DEGs from GSE8514. WGCNA analysis demonstrated that the blue module (255 genes) and turquoise module (303 genes) were significantly correlated with APA. PPI networks were then constructed. GO term enrichment analysis suggested that cellular divalent inorganic cation homeostasis, calcium ion homeostasis, collagen-containing extracellular matrix, transport vesicle and metal ion transmembrane transporter activity were the vital annotations. KEGG pathway analysis found that these genes were significantly enriched in neuroactive ligand-receptor interaction, calcium signaling pathway. Finally, we identified a total of 11 candidate genes involving in the development and progression of APA and PA. Besides, two independent datasets (GSE10927 and GSE33371) were used for external validation, and there were seven hub genes successfully verified, including C3, GRM3, AVPR1A, WFS1, PTGFR, NTSR2, and JUN. Conclusion: These newly identified genes could contribute to the understanding of potential mechanism in APA and PA and might be promising targets for the treatment of APA and PA.

15.
Cancer Manag Res ; 12: 8005-8014, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32943933

RESUMO

Purpose: To identify the relevant factors, and create and validate a predictive scoring system for the duration of laparoscopic radical prostatectomy (LRP). Patients and Methods: We retrospectively analyzed clinicopathological data from 436 patients who underwent LRP between January 2014 and January 2019, of whom 304 cases were used as a model creation group and 132 were used as a validation group. Uni/multivariate linear regression analysis was performed to determine the predictors of the duration of the procedure and a novel scoring system was created using these predictors. External validation of the scoring system was performed. The Hosmer-Lemeshow test was used to determine the goodness-of-fit of the model and calibration plots were created for visual assessment. Results: "Prolonged duration" was defined as a duration of the procedure that was longer than the mean (>150 min) duration. Multivariate analysis showed that body mass index (BMI), prostate volume, intravesicular protrusion of the prostate (IPP), the ratio of the cross-sectional areas of the prostate and the Retzius space (P/R), pelvic lymph node dissection, and neurovascular bundle (NVB) preservation were significant predictors of prolonged duration. A scoring system that included these six parameters was created and the area under the curve achieved during receiver operating characteristic analysis using this scoring system was 0.874 (95% confidence interval [CI]: 0.836-0.913). The Hosmer-Lemeshow test showed that the scoring system was well calibrated (X2=5.339, P=0.376). The external validation showed that the model had high predictive accuracy (AUC=0.835, 95% CI: 0.764-0.906) and goodness-of-fit (X2=4.401, P=0.493). Conclusion: The following factors were significantly associated with prolonged duration of laparoscopic radical prostatectomy: BMI, prostate volume, IPP, P/R, pelvic lymph node dissection, and NVB preservation. The novel scoring system created can be used to accurately predict the duration of the procedure, assess the difficulty of surgery, and improve perioperative efficiency.

16.
Front Genet ; 11: 892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922436

RESUMO

Background: Prostate cancer (PCa) is one of the most common malignant tumors worldwide. Accumulating evidence has suggested that circular RNAs (circRNAs) are involved in the development and progression of various cancers, and they show great potential as novel biomarkers. However, the underlying mechanisms and specific functions of most circRNAs in PCa remain unknown. Here, we aimed to identify circRNAs with potential roles in PCa from the PCa expression profile. Methods: We used data downloaded from the Gene Expression Omnibus to identify circRNAs that were differentially expressed between PCa samples and adjacent non-tumor samples. Relative expression levels of identified circRNAs were validated by quantitative real-time PCR. Micro (mi)RNA response elements were predicted by the CircInteractome database, and miRNA target genes were predicted by miRDB, miRTarBase, and TargetScan databases. Gene ontology (GO) enrichment analysis and pathway analysis revealed the potential biological and functional roles of these target genes. A circRNA-miRNA-mRNA interaction network was constructed by Cytoscape. The interaction between circRNAs and miRNAs in PCa was thoroughly reviewed in the PubMed. Finally, the mRNA expression of these genes was validated by the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The expression of proteins encoded by these genes was further validated by the Human protein Atlas (HPA) database. Results: A total of 60 circRNAs that were differentially expressed between PCa and healthy samples were screened, of which 15 were annotated. Three circRNAs (hsa_circ_0024353, hsa_circ_0085494, hsa_circ_0031408) certified the criteria were studied. The results of quantitative real-time PCR demonstrated that the expression of hsa_circ_0024353 was significantly downregulated in PC-3 cells when compared with RWPE-1 cells, while the expression of hsa_circ_0031408 and hsa_circ_0085494 was significantly upregulated in PC-3 cells when compared with RWPE-1 cells. GO and Kyoto Encyclopedia of Genes and Genomes analyses found that target genes were mainly enriched in metabolic processes and pathways involving phosphoinositide 3-kinase-Akt signaling, hypoxia-inducible factor-1 signaling, p53 signaling, and the cell cycle. A total of 11 miRNA target genes showing differential expression between PCa and healthy samples were selected, and their mRNA and protein expression were validated by GEPIA and HPA databases, respectively. Of these, PDE7B, DMRT2, and TGFBR3 were identified as potentially playing a role in PCa progression. Finally, three circRNA-miRNA-mRNA interaction axes were predicted by bioinformatics: hsa_circ_0024353-hsa-miR-940-PDE7B, hsa_circ_0024353-hsa-miR-1253-DMRT2, and hsa_circ_0085494-hsa-miR-330-3p-TGFBR3. Conclusion: This study identified three circRNA-miRNA-mRNA interaction axes that might provide novel insights into the potential mechanisms underlying PCa development.

17.
Front Oncol ; 10: 1547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923401

RESUMO

Objective: To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa). Methods: We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. Results: A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ≥ 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ≥ 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden. Conclusion: There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ≥ 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ≥ 3.

18.
Pathol Res Pract ; 216(10): 153109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853947

RESUMO

OBJECTIVE: To identify hub genes and pathways involved in castrate-resistant prostate cancer (CRPC). METHODS: The gene expression profiles of GSE70768 were downloaded from Gene Expression Omnibus (GEO) datasets. A total of 13 CRPC samples and 110 tumor samples were identified. The differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. Protein-protein interaction (PPI) network module analysis was constructed and performed in Cytoscape software. Weighted correlation network analysis (WGCNA) was conducted to determine hub genes involved in the development and progression of CRPC. The gene expression profiles of GSE80609 were used for validation. RESULTS: A total of 1738 DEGs were identified, consisting of 962 significantly down-regulated DEGs and 776 significantly upregulated DEGs for the subsequent analysis. GO term enrichment analysis suggested that DEGs were mainly enriched in the extracellular matrix organization, extracellular exosome, extracellular matrix, and extracellular space. KEGG pathway analysis found DEGs significantly enriched in the focal adhesion pathway. PPI network demonstrated that the top 10 hub genes were ALB, ACACB, KLK3, CDH1, IL10, ALDH1A3, KLK2, ALDH3B2, HBA1, COL1A1. Also, WGCNA identified the top 5 hub genes in the turquoise module, including MBD4, BLZF1, PIP5K2B, ZNF486, LRRC37B2. Plus, the Venn diagram demonstrated that HBA1 was the key gene in both GSE70768 and GSE80609 datasets. CONCLUSIONS: These newly identified genes and pathways could help urologists understand the differences in the mechanism between CRPC and PCa. Besides, it might be promising targets for the treatment of CRPC.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Neoplasias da Próstata/genética , Mapas de Interação de Proteínas/genética , Transcriptoma/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Masculino
19.
Cancer Cell Int ; 20: 302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32675942

RESUMO

Background: Bladder cancer (BCa) is one of the important tumors that have been proven to be treatable with immunotherapy. This study aims to identify and validate a molecular prognostic index of BCa based on immunogenomic landscape analysis. Methods: The cancer genome atlas (TCGA) database and immunology database and analysis portal (ImmPort) database were used to identified differentially expressed immune-related genes (IRGs). Prognostic IRGs were screened and protein-protein interaction (PPI) network was constructed. Multivariate Cox analysis was performed to develop a molecular prognostic index of BCa. Internal and external validation were then performed in TCGA cohort and GEO cohort, respectively. Besides, we also explore the relationship between this index and clinical characteristics, immune cell infiltration and tumor microenvironment. Results: A total of 61 prognostic IRGs were identified and a molecular prognostic index was developed. The top four hub genes included MMP9, IGF1, CXCL12 and PGF. The difference in overall survival between high-risk group and low-risk group was statistically significant. The area under curve of the receiver operating characteristic (ROC) curve was 0.757, suggesting the potential for this index. Besides, Internal validation using TCGA cohort and external validation using GEO cohort indicated that this index was of great performance in predicting outcome. T cells CD8, T cells CD4 memory activated, T cells follicular helper, macrophages M0, macrophages M2 and neutrophils were significantly associated with prognosis of BCa patients. Female, high grade, stage III&IV, N1-3 and T3-4 were associated significantly with higher risk score compared with male, low grade, stage I&II, N0 and T1-2, respectively. High risk score had a positive association with higher stromal score and ESTIMATE score while high risk score had a negative association with tumor purity. Conclusions: This study identified several prognostic immune-related genes of clinical value. Besides, we developed and validated a molecular index based on immunogenomic landscape analysis, which performed well in predicting prognosis of BCa. Further researches are needed to verify the effectiveness of this index and these vital genes.

20.
J Cancer Res Clin Oncol ; 146(8): 1953-1969, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447485

RESUMO

OBJECTIVE: Prostate cancer (PCa) is an aggressive tumor. SHC SH2-domain-binding protein 1 (SHCBP1) has been identified frequently upregulated in various cancers, in addition to PCa. The aims of this study were to determine the relationships between SHCBP1 and clinicopathological characteristics of PCa and to explore the role of SHCBP1 in PCa proliferation and progression. METHODS: Tissue microarray and immunohistochemistry were used to determine the prognostic significance of SHCBP1. The relationship between clinicopathological characteristics of PCa and SHCBP1 was then analyzed using Cox regression analyses. To investigate SHCBP1 functions in vitro and in vivo, we knocked down SHCBP1 in PCa cell lines and established xenograft mice models. A series of cytological function assays were utilized to determine the role of SHCBP1 in cell proliferation, migration, invasion, and apoptosis. RESULTS: SHCBP1 was significantly upregulated in PCa tissues compared with BPH tissues. Patients with a higher expression of SHCBP1 were associated with poor survival outcomes than those with a lower expression of SHCBP1. Lentivirus-mediated shRNA knockdown of SHCBP1 in prostate cancer cell lines diminished cell growth, migration, and invasion dramatically both in vitro and in vivo, accompanied by an enhanced expression of large tumor suppressor 1 (LATS1) and tumor protein P53 (TP53) and inhibition of MDM2 proto-oncogene (MDM2), which suggested that SHCBP1 may promote proliferation and invasion in vitro via the LATS1-MDM2-TP53 pathway. The results of cycloheximide (CHX) and MG-132 assays indicated that SHCBP1 knockdown could attenuate the degradation of TP53 by the proteasome, prolong the half-life of TP53, and enhance the stabilization of TP53. CONCLUSION: These findings suggest that SHCBP1 overexpression contributes to PCa progression and that targeting SHCBP1 might be therapeutically beneficial to patients with PCa.


Assuntos
Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Ciclo Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Bases de Dados Genéticas , Regulação para Baixo , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Masculino , Células PC-3 , Prognóstico , Neoplasias da Próstata/genética , /genética , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Adaptadoras da Sinalização Shc/biossíntese , Proteínas Adaptadoras da Sinalização Shc/genética , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
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