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BACKGROUND: Prostate cancer is the fourth most common cancer and eighth leading cause of cancer-related mortality worldwide. Its incidence is increasing in South Korea. This study aimed to investigate a predictive model for the 5-year survival probability of prostate cancer patients in a Korean primary care setting. METHOD: This retrospective study used data from the nationwide insurance claims database. The main outcome was survival probability 5 years after the initial diagnosis of prostate cancer. Potential confounding factors such as age, body mass index (BMI), blood pressure, laboratory results, lifestyle behaviors, household income, and comorbidity index were considered. These variables were available in the national health check-up information. A Cox proportional hazards regression model was used to develop the predictive model. The predictive performance was calculated based on the mean area under the receiver operating characteristic curve (AUC) after 10-fold cross-validation. RESULTS: The mean 5-year survival probability was 82.0%. Age, fasting glucose and gamma-glutamyl transferase levels, current smoking, and multiple comorbidities were positively associated with mortality, whereas BMI, alkaline phosphatase levels, total cholesterol levels, alcohol intake, physical activity, and household income were inversely associated with mortality. The mean AUC after 10-fold cross-validation was 0.71. CONCLUSIONS: The 5-year survival probability model showed a moderately good predictive performance. This may be useful in predicting the survival probability of prostate cancer patients in primary care settings. When interpreting these results, potential limitations, such as selection or healthy user biases, should be considered.
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BACKGROUND: Microsurgical free tissue transfer is the gold standard for reconstructing major bone or soft tissue defects but requires complex training, and specific resources. Therefore, some authors have stated that microsurgery is impossible in low- and middle-income countries. METHODS: Patients from Khmer underwent free flap surgery at the Children's Surgical Centre in Phnom Penh between 2004 and 2023. Two non-governmental organizations facilitated the program: Rose Charities Cambodia provided the facilities, patients and local staff, and Doctors of the World provided the surgeons, and anesthetists. At least one Khmer surgeon was trained during these operations. Digital data were collected retrospectively, and analyzed in June 2023. RESULTS: Fifty-six free flaps in 54 patients have been performed since 2004. The most frequent sites requiring reconstruction were the head and neck (35.7%), lower limbs (30.4%), and upper limbs (21.4%). The most frequent free flaps were free fibula (44.6%), gracilis (19.6%), and anterolateral thigh (16.1%). Among the 56 flaps, 41 (= 73.2%) were viable long-term and 15 (26.7%) were microsurgical failures. Sixteen flaps underwent revision in the operating room. Twenty-three flap-related complications were reported in 21 patients with mostly vascular thrombosis (n = 12), hematoma (n = 3) and infections (3). However, 83.3% had improved or were cured of their initial pathology after final surgical management. CONCLUSIONS: Free flaps performed in our series as part of international surgical collaborations in a low-income country are feasible, but we experienced higher failure rates, and later revisions compared to the results in high-income countries. We identified several solutions to improve the microsurgery outcomes in low-income settings.
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Países em Desenvolvimento , Retalhos de Tecido Biológico , Microcirurgia , Procedimentos de Cirurgia Plástica , Humanos , Camboja , Microcirurgia/métodos , Masculino , Feminino , Procedimentos de Cirurgia Plástica/métodos , Criança , Estudos Retrospectivos , Adulto , Adolescente , Pré-Escolar , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients. METHODS: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024. RESULTS: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores). CONCLUSIONS: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health.
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Neoplasias , Humanos , Neoplasias/terapia , Inteligência Artificial , Processamento de Linguagem Natural , Algoritmos , ComunicaçãoRESUMO
The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.
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BACKGROUND: Patients with renal cell carcinoma (RCC) have an elevated risk of chronic kidney disease (CKD) following nephrectomy. Therefore, continuous monitoring and subsequent interventions are necessary. It is recommended to evaluate renal function postoperatively. Therefore, a tool to predict CKD onset is essential for postoperative follow-up and management. METHODS: We constructed a cohort using data from eight tertiary hospitals from the Korean Renal Cell Carcinoma (KORCC) database. A dataset of 4389 patients with RCC was constructed for analysis from the collected data. Nine machine learning (ML) models were used to classify the occurrence and nonoccurrence of CKD after surgery. The final model was selected based on the area under the receiver operating characteristic (AUROC), and the importance of the variables constituting the model was confirmed using the shapley additive explanation (SHAP) value and Kaplan-Meier survival analyses. RESULTS: The gradient boost algorithm was the most effective among the various ML models tested. The gradient boost model demonstrated superior performance with an AUROC of 0.826. The SHAP value confirmed that preoperative eGFR, albumin level, and tumor size had a significant impact on the occurrence of CKD after surgery. CONCLUSIONS: We developed a model to predict CKD onset after surgery in patients with RCC. This predictive model is a quantitative approach to evaluate post-surgical CKD risk in patients with RCC, facilitating improved prognosis through personalized postoperative care.
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Carcinoma de Células Renais , Neoplasias Renais , Insuficiência Renal Crônica , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Nefrectomia/efeitos adversos , Estudos RetrospectivosRESUMO
We evaluated the outcomes of the Krukenberg procedure conducted for the loss of a hand secondary to an electrical burn injury in six patients (10 hands). Patient demographics, indications for surgery, surgical strategy, complications, clinical measurements and Disabilities of the Arm, Shoulder and Hand (DASH) score were recorded, in addition to subjective outcome measures, including self-perception of social acceptance and employment status. The median DASH score at follow-up was 22 (range 4-50, interquartile range 25). Patients reported recovery of useful function in operated limbs. We recommend this procedure in low-resource settings when other reconstruction is impossible.Level evidence: IV.
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Ombro , Extremidade Superior , Humanos , Resultado do Tratamento , Mãos , Amputação CirúrgicaRESUMO
Hepatic organoids might provide a golden opportunity for realizing precision medicine in various hepatic diseases. Previously described hepatic organoid protocols from pluripotent stem cells rely on complicated multiple differentiation steps consisting of both 2D and 3D differentiation procedures. Therefore, the spontaneous formation of hepatic organoids from 2D monolayer culture is associated with a low-throughput production, which might hinder the standardization of hepatic organoid production and hamper the translation of this technology to the clinical or industrial setting. Here we describe the stepwise and fully 3D production of hepatic organoids from human pluripotent stem cells. We optimized every differentiation step by screening for optimal concentrations and timing of differentiation signals in each differentiation step. Hepatic organoids are stably expandable without losing their hepatic functionality. Moreover, upon treatment of drugs with known hepatotoxicity, we found hepatic organoids are more sensitive to drug-induced hepatotoxicity compared with 2D hepatocytes differentiated from PSCs, making them highly suitable for in vitro toxicity screening of drug candidates. The standardized fully 3D protocol described in the current study for producing functional hepatic organoids might serve as a novel platform for the industrial and clinical translation of hepatic organoid technology.
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Doença Hepática Induzida por Substâncias e Drogas , Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Humanos , Diferenciação Celular/genética , OrganoidesRESUMO
The burden of malignant neoplasms is increasing worldwide. Healthy lifestyles such as maintaining a healthy body weight are important to improve survival rate in cancer patients. This study was aimed to test the hypothesis that weight change affects mortality in patients newly diagnosed with cancer. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening Cohort. A total of 1856 subjects aged at least 40 years who received a national health checkup within 6 months before cancer diagnosis was included. Study subjects were classified into 3 categories based on weight change before and after cancer diagnosis: weight loss, maintenance, and gain. Cox proportional hazards regression models were adopted to examine the association between weight change and mortality after adjusting for confounders. Compared to those experiencing weight loss, the adjusted hazards ratios (HRs) (95% confidence intervals [CIs]) for those experiencing weight maintenance were 0.327 (0.189-0.568) for all-cause mortality and 0.431 (0.215-0.867) for cancer-related mortality. The adjusted HRs (95% CIs) for those experiencing weight gain were 0.149 (0.044-0.505) for all-cause mortality and 0.289 (0.080-1.045) for cancer-related mortality. After stratifying according to baseline body mass index (BMI), weight maintenance and gain were negatively associated with all-cause mortality (0.286 [0.138-0.592] for weight maintenance and 0.119 [0.027-0.533] for weight gain) among those with a BMIâ <â 25 kg/m2. Weight maintenance and gain reduced the risk of all-cause mortality in patients newly diagnosed with any cancer. In addition, weight maintenance was significantly related to cancer-related mortality.
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Neoplasias , Redução de Peso , Humanos , Adulto , Fatores de Risco , Manutenção do Peso Corporal , Estudos Retrospectivos , Aumento de Peso , Índice de Massa Corporal , Programas Nacionais de Saúde , República da Coreia/epidemiologiaRESUMO
Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.
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Devices in the developing semiconductor market require high density, high integration, and detailed processing. Conventional wire bonding is inappropriate for fine-sized devices, and connected wires can be damaged by heat generation and external physical impact. Soldering is also used in advanced packaging technologies. However, disturbances and overhead joints can occur during bonding. Thus, sintering has been extensively utilized to overcome these drawbacks. Sintering pastes are pressurized and bonded, resulting in stable bonding during sintering. In this study, the composition of the Cu sintering material was examined using diverse additives and solvents. We manufactured sintering materials comprising Cu (1 µm), a solvent [methanol (MeOH), ethanol (EtOH), or ethylene glycol (EG)] and an acidic additive (benzoic acid, phthalic acid, or hexanoic acid). After the sintering process, the mechanical and electrical characteristics were compared to determine the optimal composition and bonding conditions. The optimum ratios between the acid and solvent were 4:6 (MeOH and EtOH) and 2:8 (EG) due to the high viscosity and effective long-term storage. All samples using EtOH as the solvent exhibited the highest sintering performances. The aromatic and carboxylic groups substantially improved the sintering performance and increased the electrical conductivity. Based on the O1s/Cu2p ratio (2.23%), the best sintering composition was EtOH/PA, which showed the highest electrical conductivity (ca. 104 S/m) and strength (34.0 MPa). The sintering process using various additives and solvents can be helpful to determine the sintering conditions while maintaining the electrical properties.
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We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77-0.94) and F1-score (range, 0.77-0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Algoritmos , Aprendizado de Máquina , República da Coreia/epidemiologia , Estudos RetrospectivosRESUMO
In this study, a broadband metasurface absorber composed of an optimal combination of copper tiles connected with four chip resistors is designed and experimentally verified. After fixing the locations of the chip resistors and setting their resistances to 100 Ω, the genetic algorithm (GA) is utilized to design the optimal copper tile pattern for broadband absorption. The optimal combination of the copper tiles is identified by determining the states of the square tile pairs between copper or air, depending on the one or zero states of the bit sequence created by GA, respectively. The full-wave simulation results of the optimized metasurface absorber confirmed a -10 dB reflectance bandwidth within the frequency range of 6.57 to 12.73 GHz for the normal incidence condition, with the fractional bandwidth being 63.83%. The accuracy of the metasurface absorber was verified through an experimental result that matched well with the full-wave simulated one.
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Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.
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BACKGROUND: There is few of optimal management guideline in elderly patients with renal cell carcinoma (RCC). To compare the survival outcomes of octogenarian RCC group and younger RCC group after surgery using nationwide multi-institutional database. METHODS: A total of 10,068 patients who underwent surgery for RCC were included in the current retrospective, multi-institutional study. A propensity score matching (PSM) analysis was conducted to control other confounding factors in analyzing survival outcomes of octogenarian and younger group RCCs. Kaplan-Meier curve analysis to calculate the survival estimates for cancer-specific survival (CSS) and overall survival (OS), and multivariate Cox-proportional hazard regression analyses to evaluate the significant variables associated with the survival outcomes were also performed. RESULTS: Both groups were well-balanced in all baseline characteristics. In a total cohort, Kaplan-Meier survival analysis showed a significantly decreased 5-year and 8-year CSS and OS in the octogenarian group compared with the younger group. However, in a PSM cohort, no significant differences were evident between the two groups in terms of CSS (5-year, 87.3% vs. 87.0%; 8-year, 82.2% vs. 78.9%, respectively, log-rank test, p = 0.964). In addition, age ≥ 80 years (HR, 1.199; 95% CI, 0.497-2.896, p = 0.686) was not a significant prognostic factor of CSS in a PSM cohort. CONCLUSIONS: The octogenarian RCC group after surgery had comparable survival outcomes compared with younger group after PSM analysis. For the life expectancy of octogenarian is getting longer, active treatment is considerable in patients with good performance status.
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Carcinoma de Células Renais , Neoplasias Renais , Idoso de 80 Anos ou mais , Humanos , Idoso , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estudos Retrospectivos , Prognóstico , Octogenários , Estadiamento de Neoplasias , República da Coreia/epidemiologiaRESUMO
To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Invasividade Neoplásica , Progressão da Doença , Fatores de RiscoRESUMO
Formalin-fixed paraffin-embedded (FFPE) tissue is the most common source of archived material for genomic medicine. However, FFPE tissue is suboptimal for high-throughput analyses, such as RNA sequencing, because the quality of nucleic acids in FFPE tissues is low. We compared RNA-seq with the nCounter system to evaluate use of FFPE tissue for genomic medicine. Twelve fresh frozen bladder cancer samples were analyzed by both RNA sequencing and nCounter, and matched FFPE samples, by nCounter. Gene-expression values obtained by these two platforms were compared by calculating Pearson correlation coefficients for each sample (across the set of matched genes) and for each matched gene (across the set of samples). For each sample, gene-expression levels measured by RNA sequencing highly correlated with those measured by nCounter (all Pearson's R > 0.8, P < 0.0001), as seen by hierarchical clustering. RNA sequencing results for fresh frozen tissues positively correlated with nCounter results for FFPE tissues (R ranged from 0.675 to 0.873, all P < 0.0001). Correlation and hierarchical-clustering analyses of nCounter data from the two specimens demonstrated a strong positive correlation between each group (R ranged from 0.779 to 0.977, all P < 0.0001). Our findings suggest that the nCounter system is useful for assaying archived-FFPE samples and that the gene-expression signatures obtained from FFPE samples represent those from fresh frozen tissues.
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RNA , Neoplasias da Bexiga Urinária , Humanos , Inclusão em Parafina/métodos , RNA/genética , Neoplasias da Bexiga Urinária/genética , Perfilação da Expressão Gênica , Transcriptoma , FormaldeídoRESUMO
BACKGROUND: Renal cell carcinoma is characterized by a late recurrence that occurs 5 years after surgery; hence, continuous monitoring and follow-up is necessary. Prognosis of late recurrence of renal cell carcinoma can only be improved if it is detected early and treated appropriately. Therefore, tools for rapid and accurate renal cell carcinoma prediction are essential. METHODS: This study aimed to develop a prediction model for late recurrence after surgery in patients with renal cell carcinoma that can be used as a clinical decision support system for the early detection of late recurrence. We used the KOrean Renal Cell Carcinoma database that contains large-scale cohort data of patients with renal cell carcinoma in Korea. From the collected data, we constructed a dataset of 2956 patients for the analysis. Late recurrence and non-recurrence were classified by applying eight machine learning models, and model performance was evaluated using the area under the receiver operating characteristic curve. RESULTS: Of the eight models, the AdaBoost model showed the highest performance. The developed algorithm showed a sensitivity of 0.673, specificity of 0.807, accuracy of 0.799, area under the receiver operating characteristic curve of 0.740, and F1-score of 0.609. CONCLUSIONS: To the best of our knowledge, we developed the first algorithm to predict the probability of a late recurrence 5 years after surgery. This algorithm may be used by clinicians to identify patients at high risk of late recurrence that require long-term follow-up and to establish patient-specific treatment strategies.
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Carcinoma de Células Renais , Neoplasias Renais , Algoritmos , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Aprendizado de Máquina , Curva ROCRESUMO
PURPOSE: Tumor microRNAs (miRNAs) are released to biofluids directly or indirectly. Although urinary miRNAs are promising non-invasive biomarkers for the diagnosis of prostate cancer (PCa), their clinical application is challenging for technical reasons. We examined the efficacy of urinary hsv2-miR-H9 to hsa-miR-3659 ratio as a non-invasive diagnostic biomarker of PCa. MATERIALS AND METHODS: The expression of urinary miRNAs was quantified by real-time PCR in 116 samples from 53 patients with benign prostatic hyperplasia (BPH) and 63 patients with PCa. The miRNA expression ratio was calculated using an upregulated miRNA (hsv2-miR-H9) as the numerator and a downregulated miRNA (hsa-miR-3659) as the denominator. RESULTS: The urinary miR-H9 to miR-3659 ratio was significantly higher in PCa than in BPH controls (p<0.001). The diagnostic accuracy of the urinary miRNA expression ratio was comparable with that of prostate-specific antigen (PSA) (receiver operating characteristic [ROC] curve comparison, p=0.287). The area under the curve for urinary miRNA expression ratio was 0.862 and that for PSA was 0.642 in the "PSA gray zone" (3-10 ng/mL) (ROC curve comparison, p=0.034). The use of the urinary miRNA expression ratio would have prevented 70.6% of unnecessary prostate biopsies; however, 28.6% of PCa cases could be missed in patients within the PSA gray zone. CONCLUSIONS: The expression ratio of urinary miR-H9 to miR-3659 could be a relevant non-invasive biomarker for PCa diagnosis, particularly for patients within the PSA gray zone.
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MicroRNAs , Hiperplasia Prostática , Neoplasias da Próstata , Biomarcadores , Humanos , Hiperplasia , Masculino , Próstata , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genéticaRESUMO
Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.