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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 , Inteligencia Artificial , Procesamiento de Lenguaje Natural , Algoritmos , ComunicaciónRESUMEN
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 Renales , Neoplasias Renales , Insuficiencia Renal Crónica , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Nefrectomía/efectos adversos , Estudios RetrospectivosRESUMEN
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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Enfermedad Hepática Inducida por Sustancias y Drogas , Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Humanos , Diferenciación Celular/genética , OrganoidesRESUMEN
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 , Pérdida de Peso , Humanos , Adulto , Factores de Riesgo , Mantenimiento del Peso Corporal , Estudios Retrospectivos , Aumento de Peso , Índice de Masa Corporal , Programas Nacionales de Salud , República de Corea/epidemiologíaRESUMEN
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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Inflammatory myofibroblastic tumors (IMTs), which are rare tumors, exhibit myofibroblastic differentiation, often with anaplastic lymphoma kinase (ALK) gene rearrangements. A subset of IMTs identified in the urinary tract have been shown to harbor a fibronectin 1 (FN1)-ALK gene fusion. In this case report, a case of an IMT with FN1-ALK fusion in the urinary bladder was presented, and its clinicopathological characteristics were reviewed. A 45-year-old female was referred to Chungbuk National University Hospital with gross hematuria. Cystoscopy revealed a solid mass in the bladder. The patient subsequently underwent transurethral resection of the lesion. The mass comprised stellate and spindled myofibroblastic cells that were arranged in loose fascicles, with a myxoid background and a mixed inflammatory infiltrate. Immunohistochemical analysis revealed that the tumor cells were positive for vimentin, cytokeratin AE1/AE3 and ALK, and focal-positive for desmin. Targeted next-generation sequencing was subsequently employed to identify the FN1-ALK fusion. To date, the patient has undergone outpatient follow-up for 18 months, with no signs of tumor recurrence. To conclude, in total, FN1 has been identified as an ALK fusion partner almost exclusively in cases of genitourinary IMTs [13 bladder IMTs (including the present case) and two uterine IMTs]. In the present case, the FN1-ALK fusion was found to involve ALK exon 19 and FN1 exon 23. By contrast, the majority of the other IMTs with an ALK fusion have involved ALK exon 20, whereas ALK fusion involving ALK exon 18 or 19 has been reported only in genitourinary IMTs. Therefore, the FN1-ALK fusion involving ALK exon 18 or 19 may be specific to a subset of IMTs arising in the urinary bladder.
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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 Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Algoritmos , Aprendizaje Automático , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
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 Renales , Neoplasias Renales , Anciano de 80 o más Años , Humanos , Anciano , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Estudios Retrospectivos , Pronóstico , Octogenarios , Estadificación de Neoplasias , República de Corea/epidemiologíaRESUMEN
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 de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Invasividad Neoplásica , Progresión de la Enfermedad , Factores de RiesgoRESUMEN
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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ARN , Neoplasias de la Vejiga Urinaria , Humanos , Adhesión en Parafina/métodos , ARN/genética , Neoplasias de la Vejiga Urinaria/genética , Perfilación de la Expresión Génica , Transcriptoma , FormaldehídoRESUMEN
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 Renales , Neoplasias Renales , Algoritmos , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/cirugía , Aprendizaje Automático , Curva ROCRESUMEN
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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MicroARNs , Hiperplasia Prostática , Neoplasias de la Próstata , Biomarcadores , Humanos , Hiperplasia , Masculino , Próstata , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genéticaRESUMEN
BACKGROUND: Snakebite-related injury is a serious public health issue. In Cambodia, it is estimated that up to 21,500 cases of envenoming occurs from snakebites annually. Musculoskeletal disability is a major long-term complication associated with the injury. In this study, we aim to describe surgical management and rehabilitation in snakebite-related musculoskeletal injuries at Children's Surgical Centre, Phnom Penh, Cambodia. METHODS: We conducted a retrospective case series analysis of patients with snakebite-related injury who were treated between January 1, 2002 and December 31, 2018. Surgical patients were divided into the early and late presenting groups (= < one year vs. > one year, respectively) based on their time interval from snake bite to time of presentation. RESULTS: There were 88 patients who presented with snakebite-related musculoskeletal injury during the cohort study period. Majority of them were male (n = 62, 71%) and had a median age of 24 years old (IQR 17-44). The injuries were all in the upper and lower limbs though lower limb injury was more common in female patients (81% vs. 48%, Fisher's test p = 0.005). The median time interval from snakebite to time of treatment was 3 years (IQR 3 months-11 years). In this study, 65 patients received surgical interventions. An ulcerated wound was the most common symptom among the early presenting group (78% vs. 24%), while scar contracture was most common among the late group (76% vs. 22%) (Fisher's test p < 0.0001). For management, surgical debridement was the most common primary intervention for the early group (52% vs. 19%), and contracture release was the most common for patients in the late group (62% vs. 15%) (Fisher's test p = 0.0004). Overall, the postoperative complication rate was highest in the late presenting group (34% vs. 3%, Fisher's test p = 0.005). CONCLUSION: More than half of the patients presented with musculoskeletal injury require surgical correction. Our study demonstrated that scar contracture is the most common complaint among the late presenting group and is associated with high postoperative complication rate.
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Mordeduras de Serpientes , Adolescente , Adulto , Cambodia/epidemiología , Niño , Cicatriz , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Retrospectivos , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/epidemiología , Adulto JovenRESUMEN
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.
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Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Anciano , Apoptosis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Ciclo Celular , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Invasividad Neoplásica , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
Approximately 80% of all new bladder cancer patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). However, approximately 15% of them progress to muscle-invasive bladder cancer (MIBC), for which prognosis is poor. The current study aimed to improve diagnostic accuracy associated with clinical outcomes in NMIBC patients. Nevertheless, it has been challenging to identify molecular biomarkers that accurately predict MIBC progression because this disease is complex and heterogeneous. Through integrative transcriptome profiling, we showed that high SKA3 expression is associated with poor clinical outcomes and MIBC progression. We performed RNA sequencing on human tumor tissues to identify candidate biomarkers in NMIBC. We then selected genes with prognostic significance by analyzing public datasets from multiple cohorts of bladder cancer patients. We found that SKA3 was associated with NMIBC pathophysiology and poor survival. We analyzed public single-cell RNA-sequencing (scRNA-seq) data for bladder cancer to dissect transcriptional tumor heterogeneity. SKA3 was expressed in an epithelial cell subpopulation expressing genes regulating the cell cycle. Knockdown experiments confirmed that SKA3 promotes bladder cancer cell proliferation by accelerating G2/M transition. Hence, SKA3 is a new prognostic marker for predicting NMIBC progression. Its inhibition could form part of a novel treatment lowering the probability of bladder cancer progression.
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PURPOSE: We aimed to determine the influence of nutritional status on urinary metabolic abnormalities and stone recurrence in patients with urolithiasis. MATERIALS AND METHODS: We analyzed data for 464 stone-formers and 464 propensity-score-matched control patients that had been collected between 2003 and 2015. Nutritional status was evaluated by use of the Controlling Nutritional Status (CONUT) score, and patients were placed into two CONUT score categories (0-1 and ≥2). Serum and 24-hour urinary metabolites were evaluated in 464 stone-formers. Kaplan-Meier and multivariate Cox regression analyses were performed to assess the influence of nutritional status on stone recurrence. Stone recurrence was defined as radiographic appearance of new stones during the follow-up period. RESULTS: Stone-formers showed a higher prevalence of poor nutrition (CONUT score ≥2) than did the propensity-score-matched control patients (p<0.001). Stone-formers who had poor nutritional status had significantly lower 24-hour urinary calcium but higher oxalate excretion (each p<0.05). Kaplan-Meier estimates demonstrated that stone-formers with poor nutritional status also experienced stone recurrence more rapidly (log-rank test, p=0.014). Multivariate Cox regression revealed that poor nutritional status was independently associated with stone recurrence (hazard ratio, 1.736; 95% confidence interval, 1.041-2.896; p=0.034). CONCLUSIONS: The CONUT score, an easily measured immunonutritional biomarker, is independently associated with a higher risk for stone recurrence in patients with urolithiasis. This implies that not only dietary excess, but also undernourished status, may be associated with aberrations in urine physicochemistry and stone recurrence.
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Estado Nutricional , Urolitiasis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. MATERIALS AND METHODS: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein-albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. RESULTS: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557-0.671; p<0.001). Patients who had a lower pretreatment AGR (<1.53) were identified as the low AGR group (n=398, 53.6%) and the remaining patients as the high AGR group (n=344, 46.4%). Preoperative AGR was significantly lower in patients with non-organ-confined disease (≥pT3) than in those with organ-confined disease (≤pT2) (p<0.001). The low AGR group had higher aggressive pathologic Gleason scores (pGS) (≥8) than did the high AGR group (p=0.016). Furthermore, the AGR was an independent prognostic factor for high pGS (≥8) and non-organ-confined disease (≥pT3), according to multivariate logistic regression analysis. CONCLUSIONS: A low AGR was closely associated with nonconfined disease (≥pT3) and high pGS (≥8). AGR can be a useful serological marker for predicting adverse pathology in patients with nonmetastatic PCa who undergo RP.