ABSTRACT
BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (Pâ =â .013) and an increased expression of vimentin (Pâ =â .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (Pâ =â .026), positive lymph node metastasis (Pâ =â .010), osseous metastasis (Pâ =â .004), and Gleason score (Pâ =â .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (Pâ =â .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.
Subject(s)
Cadherins , Parathyroid Hormone-Related Protein , Prostatic Neoplasms , Vimentin , Humans , Male , Parathyroid Hormone-Related Protein/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Prognosis , Aged , Vimentin/metabolism , Cadherins/metabolism , Middle Aged , Biomarkers, Tumor/metabolism , Immunohistochemistry , Prostate-Specific Antigen/blood , Lymphatic MetastasisABSTRACT
Clinical research has been desperately looking for effective treatments for tumors. As the molecular mechanisms of tumors have not been thoroughly defined, and the problem of anti-tumor drug resistance and clinical drug screening are not effective, new ways are currently needed to explore and improve. Given the limitations of traditional cell culture models and preclinical animal models, we review the recently developed tumor chip, a micro-physiological platform based on microfluidic technology that maximizes replication of the human TEM. Here, we focus on the design basis of the tumor microarray and its application in urology oncology, summarizing the challenges facing future development in the field. In conclusion, this review demonstrates the wide range and application of tumor chips and the potential of these systems for the future treatment and management of urological tumors.
Subject(s)
Neoplasms , Urology , Animals , Drug Evaluation, Preclinical , Humans , Lab-On-A-Chip DevicesABSTRACT
This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 (18F)-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the management of patients with prostate cancer (PCa). Relevant studies regarding 18F-PSMA PET/CT in the management of PCa published until June 1, 2021, were electronically searched in online databases including EMBASE, PubMed, and Web of Science. The primary outcome was the DR of 18F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18F-PSMA PET/CT according to Gleason scores and serum prostate-specific antigen (PSA) level. The pooled DR was calculated on a per-patient basis, with pooled odd ratios and 95% confidence intervals (CIs). In total, 17 observational studies evaluating 1019 patients with PCa met the inclusion criteria. The DR of 18F-PSMA PET/CT was 0.83 (95% CI: 0.78-0.88), in the random-effects model. Subsequently, the analysis of DR of 18F-PSMA PET/CT in PCa patients using Gleason score (≤7 vs ≥8), showed a significant difference in PCa patients. Based on the above results, the higher Gleason score of PCa patients, the higher DR of 18F-PSMA PET/CT. The DR of 18F-PSMA PET/CT in PCa was 0.57 for PSA <0.5 ng ml-1; 0.75 for PSA ≥0.5 ng ml-1 and <1.0 ng ml-1; 0.93 for PSA ≥1.0 ng ml-1 and <2.0 ng ml-1; and 0.95 for PSA ≥2.0 ng ml-1. Therefore, the significant diagnostic value was found in terms of the DR of 18F-PSMA PET/CT in managing PCa patients and was associated with Gleason score and serum PSA level.
Subject(s)
Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Fluorine Radioisotopes , Humans , Male , Neoplasm Grading , Positron Emission Tomography Computed Tomography/methods , Prostate-Specific Antigen , Prostatic Neoplasms/diagnostic imagingABSTRACT
OBJECTIVE: To discuss the clinical diagnosis and treatment of extragonadal germ cell tumor. METHODS: We analyzed the clinical data on a case of extragonadal germ cell tumor diagnosed and treated in the General Hospital of Eastern Theater Command and reviewed the relevant literature. RESULTS: The patient was initially diagnosed with retroperitoneal tumor and treated by resection of the tumor together with the left kidney due to the large volume of the tumor, which was complicated by pancreatic injury. Postoperative pathology showed it to be extragonadal germ cell malignancy. Postoperative examination revealed space-occupying lesion in the left testis, with serum alpha fetoprotein (AFP), human chorionicgonadotropin (hCG) and lactate dehydrogenase (LDH) negative, followed by stage-two resection of the left testis, which was pathologically shown with testicular seminoma. The patient received 7 courses of cisplatin, etoposide bleomycin (PEB) regimen and was followed up for 8 years, which found no recurrence or metastasis, and the patient fathered no child during the postoperative follow-up. CONCLUSION: For patients with a history of cryptorchidism and tumors located in the central axis, special attention should be paid to physical examination of the testes, testicular ultrasonography, and determination of AFP and other indicators to identify gonadal tumor metastasis. And if so, radiotherapy and chemotherapy can be considered first to reduce surgical complications and achieve accurate management.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Male , Humans , Testicular Neoplasms/diagnosis , Testicular Neoplasms/pathology , alpha-Fetoproteins/therapeutic use , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/therapy , Etoposide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Bleomycin/therapeutic useABSTRACT
MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3'-untranslated regions (3'-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.
Subject(s)
Cell Cycle Checkpoints/genetics , MicroRNAs/genetics , Microfilament Proteins/metabolism , Muscle Proteins/metabolism , Neovascularization, Pathologic/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/prevention & control , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Humans , Mice , Mice, Nude , MicroRNAs/biosynthesis , Neoplasm Invasiveness/genetics , Neoplasm Transplantation , Transplantation, HeterologousABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0170729.].
ABSTRACT
Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is a common disease with frequent occurrence in elderly men, and its incidence shows a significant positive correlation with age. Evidence has confirmed that BPH/LUTS is closely related to erectile dysfunction (ED) and significantly affects the quality of life of elderly males. Phosphodiesterase 5 inhibitors (PDE5i) can improve both ED and BPH/LUTS of the patients and PDE5 is expected to be a new therapeutic target for BPH/LUTS with ED. This review explores the structure and function of PDE5 and the action mechanisms of PDE5i so as to provide a more effective strategy for the clinical treatment of BPH/LUTS with ED.
Subject(s)
Erectile Dysfunction/drug therapy , Lower Urinary Tract Symptoms/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Prostatic Hyperplasia/drug therapy , Aged , Drug Therapy, Combination , Erectile Dysfunction/complications , Humans , Lower Urinary Tract Symptoms/complications , Male , Prostatic Hyperplasia/complications , Quality of LifeABSTRACT
OBJECTIVE: To investigate the success rate and safety of percutaneous vasoseminal vesiculography with the disposable vasographic interventional therapy kit (VITK). METHODS: This study included ninety-six 19ï¼65 (mean 43) years old male patients with infertility, hematospermia, seminal vesicle cyst, ejaculatory duct cyst, ejaculatory dysfunction, or vas deferens injury, with disease courses varying from 1 month to 7 years. With an open, multi-centered, single-group, self-controlled design and using the disposable VITK, we treated the patients by percutaneous vasoseminal vesiculography via injection of contrast medium into the vas deferens cavity under local anesthesia. RESULTS: Percutaneous vasoseminal vesiculography was successfully performed in 92 (97.87%) of the patients, which revealed abnormal seminal ducts in 51 cases (54.3%). Among the 28 infertile patients, 3 were found with bilateral and 5 with unilateral vas deferens obstruction. Vesiculitis was detected in 36 (81.8%) of the 44 hematospermia patients and bilateral vas deferens abnormality in 5 (38.5%) of the 13 patients with ejaculatory dysfunction. Transectional damage was observed in 2 patients with vas deferens injury induced by bilateral inguinal hernia repair. Three cases of seminal vesicle cyst and 4 cases of ejaculatory cyst were definitely diagnosed by vasoseminal vesiculography. CONCLUSIONS: The disposable vasographic interventional therapy kit, with the advantages of simple operation and high safety, deserves a wide clinical application in vasoseminal vesiculography.
Subject(s)
Cysts/diagnostic imaging , Genital Diseases, Male/diagnostic imaging , Infertility, Male/diagnostic imaging , Seminal Vesicles/diagnostic imaging , Vas Deferens/diagnostic imaging , Adult , Aged , Contrast Media/administration & dosage , Ejaculatory Ducts/diagnostic imaging , Hemospermia/diagnostic imaging , Hemospermia/etiology , Hernia, Inguinal/surgery , Humans , Injections , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Radiography/methods , Vas Deferens/injuries , Young AdultABSTRACT
Bladder cancer (BC) is a common urinary system tumor with high aggressiveness, and it results in relatively high mortality due to a lack of precise and suitable biomarkers. In this study, we applied the weighted gene coexpression network analysis method to miRNA expression data from BC patients, and screened for network modules associated with BC progression. Hub miRNAs were selected, followed by functional enrichment analyses of their target genes for the most closely related module. These hub miRNAs were found to be involved in several functional pathways including pathway in cancer, regulation of actin cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion and p53 signaling pathway via regulating target genes. Finally, their prognostic significance was tested using analyses of overall survival. A few novel prognostic miRNAs were identified based on expression profiles and related survival data. In conclusion, several miRNAs that were critical in BC initiation and progression have been identified in this study. These miRNAs, which may contribute to a comprehensive understanding of the pathogenesis of BC, could serve as potential biomarkers for BC prognosis or as new therapeutic targets.
ABSTRACT
OBJECTIVE: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. METHODS: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. RESULTS: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. CONCLUSION: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.
ABSTRACT
BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.
Subject(s)
Graft Rejection/pathology , Kidney Transplantation , RNA, Long Noncoding/blood , Acute Disease , Area Under Curve , Biomarkers/blood , Cohort Studies , Graft Rejection/genetics , Graft Rejection/metabolism , Humans , ROC Curve , Transcriptome , Transplantation, HomologousABSTRACT
Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.
ABSTRACT
OBJECTIVE: We conducted this meta-analysis of randomized controlled trials (RCTs) to investigate whether remote ischemic conditioning (RIC) could improve graft functions in kidney transplantation. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched to identify all eligible studies by October 5, 2016. The treatment effects were examined with risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI). The statistical significance and heterogeneity were assessed with both Z-test and Q-test. RESULTS: A total of six RCTs including 651 recipients, were eventually identified. Compared to the controls, RIC could reduce the incidence of delayed graft function (DGF) after kidney transplantation (random-effects model: RR = 0.89; fixed-effect model: RR = 0.84). However, the decrease did not reveal statistical significance. The subgroup analysis by RIC type demonstrated no significant difference among the three interventions in protecting renal allografts against DGF. Furthermore, no significant difference could be observed in the incidence of acute rejection, graft loss, 50% fall in serum creatinine, as well as the estimated glomerular filtration rate and hospital stay between the RIC and Control groups. CONCLUSIONS: This meta-analysis suggested that RIC might exert renoprotective functions in human kidney transplantation, and further well-designed RCTs with large sample size are warranted to assess its clinical efficacy.
Subject(s)
Graft Survival/physiology , Ischemic Preconditioning/methods , Kidney Transplantation , Graft Rejection/physiopathology , Humans , Immunosuppression Therapy , Kidney/injuries , Kidney/physiopathology , Kidney Function Tests , Randomized Controlled Trials as Topic , Reperfusion Injury/physiopathology , Reperfusion Injury/therapyABSTRACT
Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancers. In the present study, we identified 58 treatment-naïve primary chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide microRNA (miRNA) expression profiles, with the aim to assess the relationship of miRNA expression with the progression and prognosis of chRCC. Overall, a total of 105 miRNAs were found to be differentially expressed between tumor and the adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58 chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by the signatures. In the progression-related profiles, 27 miRNAs were selected for pathologic T and 9 for lymph node involvement. In the survival analyses, the expression levels of mir-191, mir-19a, mir-210, and mir-425 were significantly associated with both recurrence-free survival (RFS) and overall survival, while mir-210 was proven as an independent prognostic factor in terms of RFS. In summary, miRNAs are expressed differentially in chRCC, and unique expression of miRNAs is associated with the progression and prognosis of chRCC.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , MicroRNAs/genetics , Transcriptome , Adult , Aged , Biomarkers, Tumor , Carcinoma, Renal Cell/mortality , Cluster Analysis , Disease Progression , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Tumor BurdenABSTRACT
BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion. RESULTS: IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.
Subject(s)
Ischemic Preconditioning/methods , Kidney/blood supply , Reperfusion Injury/physiopathology , Animals , Hemodynamics/drug effects , Hemodynamics/physiology , Kidney/drug effects , Kidney/physiopathology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolismABSTRACT
Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.
Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Muscle Neoplasms/genetics , Muscle Neoplasms/mortality , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Aged , Carcinoma, Papillary/genetics , Carcinoma, Papillary/mortality , Carcinoma, Papillary/pathology , Disease Progression , Female , Follow-Up Studies , Gene Expression Profiling , Humans , Male , Middle Aged , Muscle Neoplasms/pathology , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Survival Rate , Urinary Bladder Neoplasms/pathologyABSTRACT
Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , MicroRNAs/biosynthesis , Age Factors , Aged , Disease Progression , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Sex FactorsABSTRACT
PURPOSE: Current evidence suggests that preconditioning with erythropoietin (EPO) can protect against ischemia reperfusion injury in rodents. However, randomized controlled trials (RCTs) assessing the efficacy and safety of high-dose EPO in kidney transplantation have yielded inconclusive results. Herein, we performed a meta-analysis of RCTs to assess whether the administration of high-dose EPO can improve graft function and the potential adverse events. METHODS: Relevant RCT studies that investigated high-dose EPO on graft function after kidney transplantation were comprehensively searched in Pubmed, Embase, and Cochrane Library until July 10, 2014. All statistical analyses were performed using Review Manager 5.0 and STATA 12.0. RESULTS: A total of 4 RCTs involving 356 patients were identified. Comprehensively, a trend of reduction in the incidence of delayed graft function could be observed in the EPO group (EPO vs. placebo groups: RR=0.88); however, the result did not reach the significance level (95% CI, 0.72-1.08; P=0.21). Furthermore, no significant difference in the incidences of adverse events was observed between the two groups. CONCLUSIONS: The current meta-analysis indicates that the administration of high-dose EPO is, to some extent, prone to protect kidney function without increasing the susceptibility to adverse events.
Subject(s)
Erythropoietin/administration & dosage , Erythropoietin/therapeutic use , Kidney Transplantation , Randomized Controlled Trials as Topic , Confidence Intervals , Dose-Response Relationship, Drug , Erythropoietin/adverse effects , Humans , Kidney Transplantation/adverse effects , Publication BiasABSTRACT
PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. METHODS: The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate, and multivariate Cox regression analyses. RESULTS: A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. CONCLUSIONS: A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , MicroRNAs/genetics , Transcriptome , Adult , Aged , Carcinoma, Renal Cell/diagnosis , Cohort Studies , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/diagnosis , Male , Microarray Analysis , Middle Aged , Organ Specificity/genetics , Prognosis , Survival AnalysisABSTRACT
Human cancers are endowed with sustained vascularization capability, and their growth, invasion, and metastasis are vascularization dependent. Recently, accumulated body of evidence suggests that endothelial progenitor cells (EPCs) can support vasculogenesis and induce angiogenesis through paracrine mechanisms. In addition, numerous clinical studies have revealed the increase in the number of EPCs in the peripheral blood of cancer patients and demonstrated the correlation of circulating EPCs (CEPCs) with the clinical outcomes. This review highlights current enrichment procedures and methods for the detection of CEPCs and different biomarkers to identify CEPCs as well as the functions of EPCs in tumor vascularization. Furthermore, we systematically review available studies on the clinical relevance of CEPCs in cancer patients to explore the potential diagnostic and prognostic values of CEPCs. Although several contrasting results exist, CEPCs can conceivably serve as a promising biomarker for the early diagnosis, prognosis prediction, and treatment response indication in the future. Additionally, further well-designed clinical studies with larger sample size and unique, specific enumeration procedures are warranted to achieve further insight into the clinical implications of CEPCs.