Predictor Of Disease Prognosis Research Articles

Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients.

Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis.

Asthma-COPD Overlap in Clinical Practice (ACO_CP 2023): Toward Precision Medicine.

Asthma and COPD have characteristic symptoms, yet patients with both are prevalent. Despite this, there is currently no globally accepted definition for the overlap between asthma and COPD, commonly referred to as asthma-COPD overlap (ACO). Generally, ACO is not considered a distinct disease or symptom from either clinical or mechanistic perspectives. However, identifying patients who present with both conditions is crucial for guiding clinical therapy. Similar to asthma and COPD, ACO patients are heterogeneous and presumably have multiple underlying disease processes. The variability of ACO patients led to the establishment of multiple definitions describing the condition's essential clinical, physiological, and molecular characteristics. ACO comprises numerous phenotypes, which affects the optimal medication choice and can serve as a predictor of disease prognosis. Various phenotypes of ACO have been suggested based on host factors including but not limited to demographics, symptoms, spirometric findings, smoking history, and underlying airway inflammation. This review provides a comprehensive clinical guide for ACO patients to be used in clinical practice based on the available limited data. Future longitudinal studies must evaluate the stability of ACO phenotypes over time and explore their predictive powers to facilitate a more precise and effective management approach.

Monocyte to High-Density Lipoprotein Ratio: A Novel Predictive Marker of Disease Severity and Prognosis in Patients With Neuromyelitis Optica Spectrum Disorders.

Background and Purpose: To investigate the association of monocyte to high-density lipoprotein ratio (MHR) with disease severity and prognosis in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods: This retrospective study included 125 patients with NMOSD. Demographic and clinical parameters, including the MHR, were assessed. The initial Expanded Disability Status Scale (EDSS) score and relapse rate were used to evaluate disease severity and prognosis, respectively. Correlations between MHR and disease severity and relapse rate were analyzed. The predictive value of MHR for prognosis was evaluated using receiver operating characteristic (ROC) curve analysis.Results: Compared with the low MHR group, the initial EDSS score (median 4.5 vs. 5.5%, P = 0.025) and relapse rate (51.61 vs. 30.16%, P = 0.015) were significantly higher in the high MHR group. MHR was positively correlated with the initial EDSS score (r = 0.306, P = 0.001). Multivariate analysis showed that MHR was significantly associated with severity (odds ratio = 7.90, 95% confidence interval [CI] = 1.08–57.82, P = 0.041), and it was a significant predictor of disease prognosis (hazard ratio = 3.12, 95% CI = 1.02–9.53, P = 0.046). The median relapse interval of the high MHR group was 24.40 months. When the MHR was higher than 0.565, the risk of relapse was high [sensitivity, 33.3%; specificity, 91.9%; area under the ROC curve, 0.642 (95% CI = 0.54–0.74, P = 0.007)].Conclusion: MHR is a novel predictive marker of disease severity and prognosis in patients with NMOSD. Early monitoring and reduction of MHR may allow earlier intervention and improved prognosis.

Serum uric acid is associated with disease severity and may predict clinical outcome in patients of pulmonary arterial hypertension secondary to connective tissue disease in Chinese: a single-center retrospective study

BackgroundPrevious studies have shown that serum uric acid (UA) levels are correlated with the severity of idiopathic pulmonary arterial hypertension (IPAH) and are predictors of disease prognosis. Still, few studies have explored the value of serum UA in pulmonary arterial hypertension secondary to connective tissue disease (CTD-PAH). This retrospective study aimed to investigate the clinical value of serum UA levels in patients with CTD-PAH.MethodsFifty CTD-PAH patients were enrolled in our study, from which baseline UA levels, respective variations, and additional clinical data were collected. The potential association between baseline UA level and severity of CTD-PAH was investigated. Furthermore, the relationship between baseline UA and survival rate of CTD-PAH patients, as well as between UA variations and survival rate of pulmonary hypertension secondary to connective tissue disease (CTD-PH) patients was discussed.ResultsBaseline serum UA levels were positively correlated with pulmonary vascular resistance (PVR). During the follow-up period, 3 CTD-PAH and 12 CTD-PH patients died. Kaplan-Meier survival curves showed lower survival rate in patients with hyperuricemia than in patients with normouricemia, in both groups (CTD-PAH group p = 0.041, CTD-PH group p = 0.013). Concerning serum UA variations, patients with persistent hyperuricemia showed the lowest survival rate when compared with patients with steady normouricemia (p = 0.01) or patients with decresing serum UA levels, i.e. undergoing from a status of hyperuricemia to a status of normouricemia (p = 0.023).ConclusionBaseline serum UA levels might predict severity of CTD-PAH. Together with baseline values, changes of uric acid level may predict the clinical prognosis of the disease.

Analysis of risk factors for post-operative complications and prognostic predictors of disease recurrence following definitive treatment of patients with esophageal cancer from two medical centers in Northwest China.

Evaluating the clinicopathological features of patients receiving definitive treatment for esophageal cancer may facilitate the identification of patterns and factors associated with post-operative complications, and enable the development of a surveillance strategy for surviving patients at a higher risk of disease recurrence. In the present study, clinical data from 579 patients with esophageal cancer that underwent radical resection of esophagus were collected. These patients were admitted to two medical centers in Northwest China, and information regarding the presence or absence of basic chronic diseases and post-operative results were retrospectively analyzed. The level of selected stem cell markers, including aldehyde dehydrogenase 1, CD133, integrin subunit α 6, integrin subunit β 4 and T-cell factor-4, were determined in esophageal cancer tissue samples in order to determine whether these markers may be useful predictors of disease prognosis and recurrence. Post-operative complications in patients receiving radical resection of the esophagus included respiratory system complications, cardiovascular abnormalities and esophageal anastomotic fistulae. Diabetes, basic respiratory disease and lower pre-surgical serum albumin levels were observed to be individual risk factors associated with post-operative complications, including respiratory system complications of acute respiratory failure and pulmonary infection, cardiovascular abnormalities of atrial fibrillation and arrhythmia, as well as the development of esophageal anastomotic fistulae. Diagnosis of esophageal cancer at later stage was significantly correlated with anastomotic fistula. Molecular detection of stem cell markers for prognosis prediction was achieved by immunohistochemical and immunofluorescence staining assays. The results demonstrated that the presence of stem-like cells in cancer tissues was associated with poor disease prognosis and a high recurrence ratio. In conclusion, the results of the current study suggested that post-operative complications were more likely to occur in patients with diabetes, basic respiratory disease or lower serum albumin levels prior to surgery. Therefore, sufficient intensive peri-operative care, rigorous operative risk assessments, and the selection of the patients with early or mid-stage esophageal cancer, may decrease the risk of post-surgical complications in patients receiving radical resection of the esophagus. In addition, a high ratio of esophageal cancer stem-like cells was associated with cancer recurrence. These results suggest that an intensive surveillance strategy should be implemented in order to facilitate early detection of disease recurrence and improve the clinical management of these patients post-surgery.

Identification of breast cancer candidate genes using gene co-expression and protein-protein interaction information.

Breast cancer (BC) is one of the most common malignancies that could threaten female health. As the molecular mechanism of BC has not yet been completely discovered, identification of related genes of this disease is an important area of research that could provide new insights into gene function as well as potential treatment targets. Here we used subnetwork extraction algorithms to identify novel BC related genes based on the known BC genes (seed genes), gene co-expression profiles and protein-protein interaction network. We computationally predicted seven key genes (EPHX2, GHRH, PPYR1, ALPP, KNG1, GSK3A and TRIT1) as putative genes of BC. Further analysis shows that six of these have been reported as breast cancer associated genes, and one (PPYR1) as cancer associated gene. Lastly, we developed an expression signature using these seven key genes which significantly stratified 1660 BC patients according to relapse free survival (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.46–0.65; Logrank p = 5.5e−13). The 7-genes signature could be established as a useful predictor of disease prognosis in BC patients. Overall, the identified seven genes might be useful prognostic and predictive molecular markers to predict the clinical outcome of BC patients.

Renal Cell Carcinoma in Children: About Two Case Report

Introduction Renal cell carcinoma (RCC) is extremely rare in children. Several factors could influence prognosis, including stage, grade, histology, symptomatic presentation, and performance status. Among these, tumor stage is the most important predictor of disease prognosis for RCC. We report our experience with two cases of children with renal cell carcinoma in children. Cases Case 1: A 13-year-old girl presented macroscopic hematuria after a right lumbar trauma. The renal ultrasonography and CT urography showed a very limited rounding medio renal mass. Fine needle renal aspiration objectified RCC. Patient underwent transabdominal radical nephrectomy. Histopathology revealed RCC grade 2 of Furhrman T1b N0 M0. The postoperative course was uneventful. Case 2: A 9-year-old girl presented macroscopic hematuria. The renal ultrasonography showed a horseshoe left kidney with limited rounding mass. CT urography showed limited left renal mass of 31 × 25 mm. Fine needle renal aspiration objectified RCC. Patient underwent transabdominal radical nephrectomy with regional lymphadenectomy. Histopathology revealed RCC associated with translocation Xp11.2 grade 2 of Furhrman T1a N1M0. The postoperative course was uneventful. Conclusion RCC is rare in children but in children older than 5 years with renal masses it is very important to suspect diagnosis. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated.

Significance of Loss of Heterozygosity in Predicting Axillary Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast

Invasive ductal carcinoma (IDC) of breast metastatic to axillary lymph node (ALN) is a critical factor in determining stage and is a strong predictor of disease prognosis and survival. We studied ALN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications. Fourteen patients with IDC with positive ALN and 19 with negative ALN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was carried out in DNA isolated from primary tumors and metastatic tumors. ALN metastasis correlated with fractional mutation rate of primary and ALN metastatic tumors, primary tumor size, and nuclear grade, and did not correlate with expression of estrogen receptor, progesterone receptor, and Her2/neu. Loss of heterozygosity (LOH) detected at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22, and 22q13 may play an important role in the development and aggressiveness of IDC, and LOHs at 1p34-36, 17p13, and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that IDC develops through various pathways that have unique and personalized patterns of mutational changes, although they share similar morphology. Detection of LOH in IDC is not only useful in studying oncogenesis, but also predicting aggressiveness and ALN metastasis.

Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk

Prostate cancer (PCa) incidence and mortality are disproportionately high among African-American (AA) men. Its detection and perhaps its disparities could be improved through the identification of genetic susceptibility biomarkers within essential biological pathways. Interactions among highly variant genes, central to angiogenesis, may modulate susceptibility for prostate cancer, as previous demonstrated. This study evaluates the interplay among three highly variant genes (i.e., IL-10, TGFbetaR-1, VEGF), their receptors and their influence on PCa within a case-control study consisting of an under-served population. This study evaluated single gene and joint modifying effects on PCa risk in a case-control study comprised of 859 AA men (193 cases and 666 controls) using TaqMan qPCR. Interaction among polymorphic IL-10, TGFbetaR-1 and VEGF was analyzed using conventional logistic regression analysis (LR) models, multi-dimensionality reduction (MDR) and interaction entropy graphs. Symbolic modeling allowed validation of gene-gene interaction findings identified by MDR. No significant single gene effects were demonstrated in relation to PCa risk. However, carriers of the VEGF 2482T allele had a threefold increase in the risk of developing aggressive PCa. The presence of VEGF 2482T combined with VEGFR IVS6 + 54 loci were highly significant for the risk of PCa based on MDR and symbolic modeling analyses. These findings were substantiated by 1,000-fold cross validation permutation testing (P = 0.04), respectively. These findings suggest the inheritance of VEGF and VEGFR IVS6 + 54 sequence variants may jointly modify PCa susceptibility through their influence on angiogenesis. Larger sub-population studies are needed to validate these findings and evaluate whether the VEGF-VEGR axis may serve as predictors of disease prognosis and ultimately clinical response to available treatment strategies.

PROGNOSIS OF LIFE IMPROVEMENT AFTER LIVING-RELATED RENAL TRANSPLANTATION BY ANALYSIS OF HEART RATE VARIABILITY IN LONG-TERM ELECTROCARDIOGRAM

P324 Aims: Despite recent advances in hemodialysis techniques and medical management for end-stage renal disease (ESRD), mortality is still high among chronic hemodialysis patients. In such patients, cardiovascular complications are leading cause of death. Analysis of heart rate dynamics (R-R intervals) using a long-term electrocardiogram provides prognostic information for patients under various clinical situations. Decreased heart rate variability (HRV) predicts the risk for cardiac death in patients with ESRD. There is no data on prognosis of life after renal transplantation compared to before, using 24 hours HRV analysis. The purpose of this study is to determine therapeutic value of renal transplantation on prognosis of life, by HRV using 24 hours electrocardiogram in a prospective analysis in ESRD patients. Methods: Between March 2002 and May 2003, out of 36 patients before living-related renal transplantation in our department, 24 were enrolled in this study. We excluded 12 patients because of diabetes mellitus, s-Cre>2mg/dl at 6 months, treatment with βblocker before or after transplantation. 24 patients (15 male, 9 female) were aged 37±11 years. Before transplantation, they had been on hemodialysis for 5.3±6.8 years. 4 patients were preemptive. 24 hours electrocardiogram was performed at before operation which is in a dialysis-free day of the middle week, 1month, 6months, 12months after operation. All recordings were made in hospitalization. We used Nihon Kouden RAS3102 as a 24 hours electrocardiogram, and after distinguishing QRS complex, we analyzed it by using MemCalc®. Results: Standard deviation of all R-R intervals during 24 hours (SDNN) which is a predictor of disease prognosis was improved from 115.5±33.1 ms to 151.3±34.3 ms (p=0.0004) significantly in 6 months after transplantaion, and HRV triangular index (total number of all R-R intervals divided by the height of the histogram of R-R intervals measured on a discrele scale with bins of 7.8125 ms) as a predictor of disease prognosis was significantly improved from 33.4±11.4 to 42.7±10.3 (p=0.0013) in 6 months after transplantaion. Power of high frequency band (HF) as a predictor of parasympathetic function and power of low frequency band (LF)/HF as a predictor of sympathetic function had a tendency to improve from 128.7±115.4 ms2 to 232.7±270.2 ms2 (p=0.07), from 8.0±9.9 to 4.6±2.8 (p=0.07) respectively in 6 months after transplantaion, but not significant. Power of ultra low frequency (ULF) and power of very low frequency (VLF), which are predictors of disease prognosis, were improved from 3065±1370 ms2 to 4861±2033 ms2 (p=0.0008), 1439±825 ms2 to 2150±836 ms2 (p=0.0013) respectively in 6 months after transplantaion. All predictors but SDNN and ULF were not significantly improved in a month after transplantation. Conclusions: Prognosis of life under chronic hemodialysis is dramatically improved from just 6 months after renal transplantation. This improvement is earlier than recovery of autonomic function.

Plasma bcl-2 and nitric oxide: possible prognostic role in patients with metastatic breast cancer.

Interest in translational studies on breast cancer is presently devoted to identifying biological predictors of disease prognosis and response to treatment. In this study, we determined the plasma levels of bcl-2 and nitric oxide in 45 patients with metastatic breast cancer using an ELISA technique and correlated them with clinical and biological factors that may affect the outcome of disease. The results were as follows. The mean level of bcl-2 was 278.44 +/- 383.2 U/L compared with 64.42 +/- 14.4 U/L (p = 0.007) for controls. Levels of bcl-2 were higher in patients less than 50 yr old, premenopausals., GIII tumors, positive nodes, ER positive tumors (p = 0.6, 0.5, 0.9, 0.4, and 0.005, respectively). The site of metastatic disease and the number of metastatic sites did not show statistically significant influences over bcl-2 levels. Furthermore, there was a trend, although not significant, toward improvement of survival in patients with higher levels of bcl-2. The mean level of the nitric oxide (NO) was 297.12 +/- 220.54 microM compared with 13.91 +/- 1.1 microM for controls (p = 0.003). The levels were higher in patients over 50 yr, postmenopausal patients, those with visceral deposits, grade III tumors, positive lymph nodes, and those with disease-free survival of less than 6 mo following primary treatment (p = 0.1, 0.2, 0.1, 0.09, 0.4, and 0.08 respectively). Furthermore, there was no correlation between NO levels and survival (r = 0.002). This study demonstrates a potential role for NO and bcl-2 as prognostic factors in patients with metastatic breast cancer. However, larger studies with more patients together with a comparison of serum levels (ELISA) and tissue levels (MOAb) are still required.