Subject(s)
COVID-19 , Lactams , Leucine , Nitriles , Proline , Humans , Ritonavir/therapeutic use , COVID-19 Drug TreatmentABSTRACT
With the rapidly growing body of medical knowledge, physicians must engage in lifelong learning. Physicians' orientation toward lifelong learning is of crucial importance. This study aimed to explore the effects of job characteristics on physicians' lifelong learning. A multicenter study collecting data from physicians from three medical centers in Taiwan was performed. A total of 321 physicians were surveyed with the Chinese version of the Job Content Questionnaire (C-JCQ) and the revised Jefferson Scale of Physician Lifelong Learning (JeffSPLL) to assess their job characteristics (i.e., job demands, job control, social support) and orientation toward lifelong learning. Exploratory factor analysis was employed to validate both questionnaires. Hierarchical regression was utilized to explore the relationship of job characteristics and predictors with physicians' lifelong learning. The results revealed that job demands (ß = 0.10), job control (ß = 0.19), social support from supervisors (ß = 0.16), the interaction of job demands × job control (ß = - 0.11) and the interaction of job demands × social support from colleagues (ß = 0.13) were significantly (p < .05, p < .001) related to lifelong learning. Moreover, physicians in the active group (high demand, high control) possessed a stronger orientation toward lifelong learning (mean = 3.57) than those in the low-strain group (mean = 3.42), high-strain group (mean = 3.39) and passive group (mean = 3.20). In conclusion, examining physicians' job demands, job control and social support helps us to understand their orientation toward lifelong learning and may provide insight to improve educational strategies.
Subject(s)
Education, Continuing , Physicians , Humans , Social Support , Job Description , Surveys and Questionnaires , Job SatisfactionABSTRACT
Advance care planning (ACP) and advance directives (ADs) ensure patient autonomy in end-of life care. The number of ADs made and followed in Taiwan is still lacking. This study aimed to determine the factors that influence the willingness to participate in ACP among outpatients in Taiwan. In this study, we conducted a cross-sectional survey based on convenient sampling methods. The questionnaire included questions about participants' basic sociodemographic information, knowledge of ACP, and awareness of ACP. A total of 198 adults who were outpatients of a family medicine clinic in an affiliated hospital in Taiwan were recruited. The associations between each variable were evaluated using the χ2 test. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression method to examine the influence of each variable on willingness to participate in ACP. Being happy and being a healthcare professional were positively correlated with ACP participation. A lack of ACP knowledge (OR = 0.30 in model A and OR = 0.42 in model C), valuing "Reducing families' end-of-life decision-making burden" (OR = 2.53 in model B and OR = 2.65 in model C), and a "Belief in a good death" (OR = 4.02 in model B and OR = 4.10 in Model C) were the main factors affecting subjects' willingness to participate in ACP. Knowing which factors influence willingness to participate in ACP helps in the promotion of ACP. Continuously educating both the general public and healthcare professionals strengthens knowledge about the right to autonomy, about its associated laws, and about the ACP process, and thus, programs should be created to provide this education. Additionally, taking into account the differences between cultures can be helpful.
Subject(s)
Advance Care Planning , Outpatients , Adult , Cross-Sectional Studies , Humans , Pilot Projects , TaiwanABSTRACT
ABSTRACT Background: The rapid outbreak of COVID-19 pandemic promptly changed people's daily lives, influenced human interactions and economic activities and induced mental reactions. Objective: This review synthesized the evidence of correlation between demographic factors, social media exposure, stressors and anxiety and depression status in the early phase of COVID-19. Method: A systematically search included observational studies published before May15, 2020. We selected studies designed with valid measuring instruments of anxiety and depression. Result: 20 articles were included (19 cross-sectional) for review. People who were divorced/widowed, with poor self-rated health status, chronic illness and previous psychiatric illness had higher anxiety and depression prevalence. Higher COVID-19 awareness (including COVID-19 knowledge and precautionary measure) decreased anxiety and depression. The protective measures to reduce anxiety and depression levels included avoiding sharing meals, frequently washing hands and wearing mask. Economic loss, academic delay, influence of daily life, worrying and symptoms related to infection were stressors of anxiety and depression. There were lots of inconsistent results due to convenience sampling and diverse measuring instrument. Conclusion: Our review suggested that reliable information from health authorities, enhancing health literacies and prevention measures of general population can reduce anxiety and depression levels.
ABSTRACT
BACKGROUND AND AIMS: Thrombomodulin (TM) is an endothelial cell membrane-bound anticoagulant protein expressed in normal arteries. After vascular injury, medial and neointimal smooth muscle cells (SMCs) exhibit large amounts of TM. The purpose of this study was to investigate the physiological significance of vascular SMC-bound TM. METHODS: The morphology, expression of phenotype markers and cell behaviors of cultured aortic SMCs after knockdown of TM were observed. Transgenic mice with SMC-specific TM deletion were generated, and carotid neointima formation was induced by carotid ligation. RESULTS: Cultured human aortic SMCs displayed a synthetic phenotype with a rhomboid-shaped morphology and expressed TM. TM knockdown induced a spindle-shaped change in morphology with an increased expression of contractile phenotype marker and decreased expression of synthetic phenotype marker. TM knockdown not only attenuated the proliferation of SMCs but also reduced tumor necrosis factor-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/TMflox/flox mice at 4 weeks after ligation. CONCLUSIONS: Our results indicate that vascular SMC-bound TM plays a role in changes of the SMC phenotype. It also influences SMC cell behavior and injury-induced neointima formation.
Subject(s)
Carotid Artery Injuries/genetics , Gene Expression Regulation , Muscle, Smooth, Vascular/pathology , Neointima/pathology , Thrombomodulin/genetics , Animals , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Injuries/metabolism , Carotid Artery Injuries/pathology , Cell Membrane/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Muscle, Smooth, Vascular/metabolism , Neointima/metabolism , Phenotype , RNA/genetics , Thrombomodulin/biosynthesisABSTRACT
This study was undertaken to assess the effect of blood glucose on BMD and interactions with age, sex, and BMI in a Taiwanese population. Both obese and non-obese people with type 2 diabetes (T2DM) had higher BMD, at lumbar spine and femoral neck, compared with healthy subjects. In addition, the prevalence of osteoporosis significantly decreased with blood sugar and HbA1c. PURPOSE: This study was undertaken to assess the effect of blood glucose on BMD and possible interactions with age, sex, and BMI in a Taiwanese population. PATIENTS AND METHODS: This study was a retrospective cross-sectional study using data from the Health Examination Database of Changhua Christian Hospital. Data on BMD of the lumbar spine and femoral neck were obtained by dual X-ray absorptiometry (DXA), and other relevant clinical and laboratory data were recorded. RESULTS: The type 2 diabetes (T2DM) group had a higher BMD than the controls. When comparing the prevalence of osteoporosis between subjects by glucose and HbA1c level, the prevalence of osteoporosis significantly decreased with blood glucose and HbA1c. In addition, the BMD of the lumbar spine and femoral neck was higher in the T2DM group than in the controls. Osteoporosis was negatively associated with DM, BMI, and drinking, but positively associated with age, female gender, previous fracture history, and other diseases of the musculoskeletal system and connective tissue. The association between diabetes and osteoporosis remained statistically significant after adjusting for the above factors. T2DM was associated with lower odds of osteoporosis in both obese (OR = 0.77) and non-obese (OR = 0.63) (p for interaction = 0.555). CONCLUSIONS: Both obese and non-obese people with T2DM had higher BMD, at lumbar spine and femoral neck, compared with healthy subjects. In addition, the prevalence of osteoporosis significantly decreased with blood glucose and HbA1c.
Subject(s)
Absorptiometry, Photon/statistics & numerical data , Blood Glucose/analysis , Bone Density , Diabetes Mellitus, Type 2/physiopathology , Osteoporosis/epidemiology , Adult , Age Factors , Aged , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Female , Femur Neck/diagnostic imaging , Glycated Hemoglobin/analysis , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Obesity/blood , Obesity/complications , Obesity/physiopathology , Osteoporosis/etiology , Prevalence , Retrospective Studies , Sex Factors , Taiwan/epidemiologyABSTRACT
BACKGROUND PCDH8 is a newly-discovered suppressor gene that is frequently inactivated by aberrant methylation in several human cancers, including prostate cancer. The identification of PCDH8 methylation can be used as a potential predictive biomarker. Prostate cancer patients with high Gleason score are considered as being at high risk for tumor recurrence and progression, and adjuvant therapy is often routinely performed in clinical practice. In the present study, we did not measure the methylation of PCDH8 in these patients. The main purpose of the present study was to evaluate the clinical significance of PCDH8 methylation in serum of prostate cancer patients with low Gleason score. MATERIAL AND METHODS PCDH8 methylation in serum samples of 117 patients and 47 controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8 methylation status with the clinicopathological parameters of prostate cancer patients with low Gleason score and patient outcomes. RESULTS We found that PCDH8 was more frequently methylated in serum samples of patients with prostate cancer than in controls. PCDH8 methylation was correlated with advanced clinical stage (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse biochemical recurrence (BCR)-free survival (P<0.001) than patients without. Independent prognostic factors for worse BCR-free survival of prostate cancer patients with low Gleason score were: PCDH8 methylation in serum (Exp (B)=3.147, 95% CI: 1.152-7.961, P=0.007), clinical stage (Exp (B)=2.53, 95% CI: 1.032-4.763, P=0.025) and lymph node status (Exp (B)=1.476, 95% CI: 1.107-4.572, P=0.042). CONCLUSIONS Our study indicated that PCDH8 methylation in serum occurred frequently in prostate cancer patients and was correlated with risk factors for poor outcome. The methylation of PCDH8 in serum is a potential predictive marker for prostate cancer patients with low Gleason score after surgery.
Subject(s)
Cadherins/genetics , Prostatic Neoplasms/genetics , Aged , Biomarkers, Tumor/genetics , Cadherins/blood , Cadherins/metabolism , Case-Control Studies , DNA Methylation/genetics , DNA Methylation/physiology , Disease Progression , Disease-Free Survival , Humans , Male , Middle Aged , Neoplasm Grading/methods , Neoplasm Recurrence, Local/genetics , Prognosis , Promoter Regions, Genetic/genetics , Prostatectomy , Prostatic Neoplasms/diagnosis , Protocadherins , Risk FactorsABSTRACT
BACKGROUND Current studies indicated that PCDH17 functions as a tumor suppressor, which is frequently inactivated by aberrant promoter methylation in urologic tumors. The main purpose of this study was to investigate the methylation status of PCDH17 in serum and its clinical significance in renal cell carcinoma (RCC). MATERIAL AND METHODS The methylation status of PCDH17 in serum samples of 142 RCC patients and 34 controls was evaluated by methylation-specific PCR (MSP). Then we correlated PCDH17 methylation status with the clinicopathologic features of RCC patients and patient outcomes. RESULTS We found that PCDH17 was more frequently methylated in RCC patients than in controls. Moreover, PCDH17 methylation in serum was significantly correlated with advanced stage (p=0.044), higher grade (p=0.019), lymph node metastasis (p=0.008) and tumor progression (p<0.001). In addition, patients with methylated PCDH17 had shorter progression-free survival (p<0.001) and overall survival (p=0.017) than patients without, and PCDH17 methylation in serum was an independent prognostic factor for worse progression-free survival (HR: 4.215, 95% CI: 1.376-9.032, p<0.001) and overall survival (HR: 5.092, 95% CI: 1.149-12.357, p=0.046) of patients with RCC. CONCLUSIONS The present study indicates that PCDH17 methylation in serum is a frequent event in RCC and associated with risk factors of poor outcomes. Moreover, PCDH17 methylation in serum is a potential prognostic biomarker for patients with RCC after surgery.
Subject(s)
Cadherins/genetics , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/genetics , DNA Methylation/genetics , Kidney Neoplasms/blood , Kidney Neoplasms/genetics , Promoter Regions, Genetic , Aged , Cadherins/blood , Disease-Free Survival , Female , Humans , Male , Middle Aged , Multivariate AnalysisABSTRACT
Bladder cancer is a heterogeneous disease with outcome difficult to predict, and novel predictive biomarkers are needed. PCDH7, a member of protocadherins family, functions as tumor suppressor in several human cancers. The human PCDH7 gene is localized in chromosome 4p15, which is often inactivated in human cancers, including bladder cancer. The aim of this study was to investigate the clinical significance of PCDH7 expression in non-muscle invasive bladder cancer (NMIBC). PCDH7 expression was examined using immunohistochemical staining in 199 primary NMIBC tissues and 25 normal bladder epithelial tissues. Then the relationship between PCDH7 expression and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis was used to evaluate the correlation between PCDH7 expression and prognosis. PCDH7 expression in NMIBC tissues was significantly lower than that in normal bladder epithelial tissues (P < 0.001). Low PCDH7 expression correlated with advanced grade (P = 0.021) and larger tumor size (P = 0.044). Moreover, patients with low PCDH7 expression have shorter recurrence-free survival (P < 0.001), progression-free survival (P = 0.007) and overall survival (P = 0.011) than patients with high PCDH7 expression. Low PCDH7 expression is an independent predictor of recurrence-free survival (multivariate Cox analysis: P = 0.007), progression-free survival (multivariate Cox analysis: P = 0.014) and overall survival (multivariate Cox analysis: P = 0.004). The findings indicate that low PCDH7 expression is a potential prognostic biomarker for primary NMIBC.
Subject(s)
Biomarkers, Tumor/analysis , Cadherins/biosynthesis , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Cadherins/analysis , Carcinoma, Transitional Cell/mortality , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Protocadherins , Urinary Bladder Neoplasms/mortalityABSTRACT
PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.
Subject(s)
Chemokines, CXC/genetics , Gene Expression Regulation, Neoplastic/drug effects , Prostatic Neoplasms/genetics , RNA, Messenger/metabolism , Receptors, Interleukin-8B/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Chemokines, CXC/metabolism , Chemokines, CXC/pharmacology , Epithelial Cells/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Prostate/cytology , Prostate/metabolism , Prostatic Neoplasms/metabolism , Receptors, Interleukin-8B/metabolism , Stromal Cells/metabolism , Tumor Protein p73/genetics , bcl-2-Associated X Protein/geneticsABSTRACT
BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.
Subject(s)
Cadherins/blood , Prostatic Neoplasms/blood , Aged , Disease-Free Survival , Humans , Male , Methylation , Multivariate Analysis , Polymerase Chain Reaction , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prostatectomy , Prostatic Neoplasms/surgery , ProtocadherinsABSTRACT
BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy. MATERIAL AND METHODS We evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR. RESULTS The ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy. CONCLUSIONS PCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy.
Subject(s)
Biomarkers, Tumor/blood , Cadherins/blood , Neoplasm Recurrence, Local , Prostatectomy , Prostatic Neoplasms/pathology , Aged , Humans , Male , Methylation , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgeryABSTRACT
DNA methylation is one of the major mechanisms via which tumor suppressor gene inactivation occurs. For example, hypermethylation of the promoter region of cadherin 11 (CDH11), a novel tumor suppressor gene, frequently occurs in human cancer. In the current study, the methylation status of CDH11 was investigated in bladder cancer tissue samples, and the correlation with clinicopathological features and patient outcome was assessed. The methylation status of CDH11 was detected in 146 bladder cancer tissues and 37 normal bladder epithelial tissues using methylation-specific polymerase chain reaction (PCR). In addition, CDH11 mRNA expression levels were examined by quantitative PCR. Subsequently, associations between CDH11 methylation and specific clinicopathological characteristics, as well as patient outcome, were analyzed. Aberrant CDH11 promoter hypermethylation was detected in 63.0% (92/146) of bladder cancer tissues, however, no CDH11 methylation was identified in the control samples; this difference was significant (P<0.05). Furthermore, CDH11 mRNA expression levels were significantly lower in the tumor samples with methylated CDH11 compared with the normal bladder epithelium and tumor samples with unmethylated CDH11 (P<0.05). When the methylation status of CDH11 was correlated with the clinicopathological features, it was identified that CDH11 methylation was significantly associated with poor differentiation (P=0.0440), an advanced disease stage (P=0.0350), a larger tumor size (P=0.0013) and multiple tumors (P=0.0390). In addition, patients with methylated CDH11 exhibited significantly poorer outcomes than patients with unmethylated CDH11 (P=0.0004). Furthermore, multivariate Cox proportional hazard analysis indicated that CDH11 methylation was independently associated with a poor outcome in the patients with bladder cancer, with a relative risk of mortality of 6.852 (P=0.0082; 95% confidence interval, 3.461-16.177). The current findings indicate that aberrant CDH11 methylation frequently occurs in bladder cancer, and correlates with malignant behavior and poor outcome. Thus, CDH11 methylation status may be used as an independent prognostic biomarker for patients with bladder cancer.
ABSTRACT
BACKGROUND: Protocadherin17 (PCDH17) is a tumor suppressor gene, and is frequently silenced by promoter methylation in human cancers, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of PCDH17 methylation in ccRCC remains largely unclear. The aim of the present study was to investigate the methylation status of PCDH17 in ccRCC and its potential relevance to clinicopathological parameters and prognosis. MATERIAL AND METHODS: Methylation-specific PCR was used to examine the methylation status of PCDH17 in 191 ccRCC tumors and matched paired adjacent noncancerous tissues. Subsequently, the associations between PCDH17 methylation and clinicopathological parameters and prognosis of patients with ccRCC were analyzed. RESULTS: PCDH17 methylation occurred in 66.5% of ccRCC tumors, but in only 12.1% of adjacent noncancerous tissues. PCDH17 methylation is significantly correlated with advanced stage, higher grade, and lymph node metastasis in ccRCC. Moreover, it is an independent prognostic factor for progression-free survival and overall survival of patients with ccRCC. CONCLUSIONS: PCDH17 methylation occurred more frequently and was associated with malignant clinicopathological characteristics and poor prognosis in ccRCC patients. Thus, PCDH17 methylation may be used as a novel biomarker to predict the prognosis of patients with ccRCC.
Subject(s)
Cadherins/genetics , Carcinoma, Renal Cell/genetics , DNA Methylation , Kidney Neoplasms/genetics , Promoter Regions, Genetic , Aged , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/metabolism , CpG Islands , Disease-Free Survival , Female , Humans , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/metabolism , Lymphatic Metastasis , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: Protocadherin8 has been demonstrated to play critical roles in initiation and progression of several human cancers. It is frequently inactivated by promoter methylation in cancers and may be used as a potential biomarker. However, the methylation status of protocadherin8 and its clinical significance in prostate cancer remains largely unknown. The purpose of this study was to evaluate the clinical significance of protocadherin8 methylation in early-stage prostate cancer. MATERIAL AND METHODS: The promoter methylation status of protocadherin8 in 162 prostate cancer tissues and 47 normal prostate tissues was examined using methylation-specific PCR (MSP). Subsequently, the relationships between protocadherin8 methylation and clinicopathological features of prostate cancer patients and biochemical recurrence-free survival of patients were analyzed. RESULTS: We found that protocadherin8 methylation occurred frequently in prostate cancer tissues but not in normal prostate tissues. Moreover, protocadherin8 methylation was significantly associated with advanced pathologic stage, higher level of preoperative prostate specific antigen (PSA), higher Gleason score, positive lymph node metastasis, and biochemical recurrence. In addition, patients with protocadherin8 methylated have shorter biochemical recurrence-free survival time than patients without. Multivariate Cox regression analysis revealed that protocadherin8 methylation was an independent predictor of biochemical recurrence-free survival in prostate cancer patients. CONCLUSIONS: Promoter methylation of protocadherin8 is a frequent event in prostate cancer, and might be used as an independent prognostic factor for biochemical recurrence-free survival in patients with prostate cancer.
Subject(s)
Cadherins/genetics , DNA Methylation/genetics , Neoplasm Recurrence, Local/genetics , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Aged , Disease-Free Survival , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , ProtocadherinsABSTRACT
BACKGROUND: PCDH8 is a tumor suppressor that regulates cell adhesin, proliferation, and migration. It is often inactivated by aberrant promoter methylation in several human cancers, including clear cell renal cell carcinoma (CCRCC). The clinical significance of PCDH8 methylation in CCRCC remains unclear. The aim of this study was to investigate the relationship between PCDH8 methylation and clinicopathological characteristics as well as outcome of patients with CCRCC. MATERIAL/METHODS: The methylation status of PCDH8 in 153 CCRCC tissues and 97 paired adjacent normal renal tissues were examined using methylation-specific PCR (MSP). Then the relationships between PCDH8 methylation and clinicopathological features as well as progression-free survival of CCRCC patients were evaluated. RESULTS: PCDH8 methylation was significantly more frequent in CCRCC tissues compared with normal renal tissues. Moreover, PCDH8 methylation was significantly correlated with advanced clinical stage (P=0.0141), higher grade (P=0.0190), and lymph node metastasis (P=0.0098). In addition, multivariate analysis showed that PCDH8 methylation was independently associated with poor progression-free survival (P=0.0316). CONCLUSIONS: PCDH8 methylation is a frequent event in CCRCC and is correlated with unfavorable clinicopathological features. Moreover, PCDH8 methylation may be a useful biomarker to predict the progression of CCRCC.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , DNA Methylation/genetics , Kidney Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Cadherins/genetics , Carcinoma, Renal Cell/pathology , Disease-Free Survival , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Protocadherins , Treatment OutcomeABSTRACT
BACKGROUND: CDH13 is a novel tumor suppressor gene often inactivated by aberrant promoter methylation in human cancers. Previous studies have shown that CDH13 methylation correlated with advanced disease and poor prognosis in non-muscle invasive bladder cancer (NMIBC). The aim of the current study was to investigate the correlations between CDH13 methylation and disease recurrence as well as progression of NMIBC. MATERIAL AND METHODS: The methylation status of CDH13 in 178 NMIBC samples and 38 normal bladder epithelial tissues was examined by methylation-specific PCR (MSP), and then correlated with clinicopathological features. RESULTS: We found that CDH13 methylation occurs frequently in NMIBC, and significantly correlates with high grade, advanced stage, larger tumor size, and tumor recurrence and progression. Moreover, patients with methylated CDH13 exhibited significantly shorter recurrence-free survival (P<0.0001) and progression-free survival (P=0.0060) than patients with unmethylated CDH13. In addition, a multivariate Cox proportional hazard model analysis suggests that CDH13 methylation is an independent predictor for the recurrence (P=0.0043) and progression (P=0.0016) of NMIBC after initial transurethral resection. CONCLUSIONS: Our findings demonstrate that CDH13 methylation is a frequent event in NMIBC, and is associated with unfavorable tumor features. It should be used as an independent predictor for the recurrence and progression of NMIBC, and may be useful for the design of individualized therapeutic modalities.
Subject(s)
Biomarkers, Tumor/genetics , Cadherins/genetics , DNA Methylation/genetics , Disease Progression , Muscles/pathology , Neoplasm Recurrence, Local/diagnosis , Urinary Bladder Neoplasms/genetics , Aged , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Proportional Hazards Models , Time FactorsABSTRACT
BACKGROUND: Aberrant methylation of protocadherin 17 (PCDH17) has been reported in several human cancers. However, the methylation status of PCDH17 in prostate cancer and its clinical significance remains unclear. The aim of this study was to investigate the methylation status of PCDH17 and its clinical significance in patients with prostate cancer after radical prostatectomy. MATERIAL/METHODS: The methylation status of PCDH17 in 152 prostate cancer tissues and 51 non-tumoral prostate tissues was examined by methylation-specific PCR (MSP). Then the association between PCDH17 methylation and clinicopathologic parameters was analyzed. Kaplan-Meier survival analysis, log-rank test and multivariate Cox proportional hazard model analysis were used to analyze the correlation between PCDH17 methylation and prognosis of patients with prostate cancer. RESULTS: Our data demonstrated that PCDH17 methylation occurred frequently in prostate cancer. PCDH17 methylation was significantly associated with higher pathological Gleason score (P=0.0315), advanced pathological stage (P=0.0260), higher level of preoperative PSA (P=0.0354), positive angiolymphatic invasion (P=0.0461), positive lymph node metastasis (P=0.0362), and biochemical recurrence (BCR) (P=0.0018). In addition, PCDH17 methylation was an independent predictor of poor biochemical recurrence-free (BCR-free) survival and overall survival for patients with prostate cancer. CONCLUSIONS: PCDH17 methylation is a frequent tumor-specific event in prostate cancer, and is significantly correlated with shorter BCR-free survival and overall survival of patients with prostate cancer after radical prostatectomy. PCDH17 methylation in tumor samples after radical prostatectomy may be used as an independent prognostic biomarker.