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Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS).

Prospective analysis of the importance of the plasma levels of beta-2 microglobulin (B2M) in 553 patients with myelodysplastic syndrome (MDS) found that B2M is an independent prognostic variable for survival with weighted significance second only to the karyotype. The incorporation of the B2M covariate into risk assessment of MDS patients added significantly to the power of the IPSS to stratify MDS patients into risk categories. Our results further document that the 2 objectively measured covariates that display the highest power to predict survival, that is, karyotype and B2M, can alone be used for risk stratification. While the results must be verified in an independent and comparable population, our data strongly recommend routine measurement of B2M in patients with MDS.

Female↗

[Enhanced prognostic stratification of cad patients with dilated left ventricle by stress and rest functional parameters and 99mTc-tetrofosmin Gated-SPECT].

PURPOSE: To evaluate whether the post-stress and rest functional parameters, measured by Gated-SPECT, have incremental prognostic value compared with perfusion parameters in predicting cardiac events (CE), in a population of CAD patients with dilated LV. MATERIALS AND METHODS: A total of 670 consecutive patients (mean age: 62; range 29-86 yrs.) underwent conventional diagnostic 2-day gated-SPECT with 99mTc-tetrofosmin (55% exercise stress test, 45% dip stress): 605 patients (mean age: 62 yrs., range: 34-86 yrs.) had known or suspected CAD, whereas 65 (mean age: 60 yrs, range: 29-80 yrs) had low pre-test likelihood of CAD (<10%), a normal post-stress perfusion scan and no hypertension. Fifty-three percent of CAD patients had a history of MI. Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0=normal, 4=no uptake), while wall thickening was assessed visually on stress/rest end-systolic images using a 4-point score (0=normal, 3=absence of WT). LVEF and volumes were calculated using an automatic algorithm. Post-stress and rest ratio were determined for both end-diastolic and end-systolic volume, while the post-stress LVEF change (d-LVEF) was calculated according to the following formula: (Stress LVEF-rest LVEF)/rest LVEF*100. RESULTS: By using a cutoff value of 126 ml for rest-EDV, and of 68 ml for rest-ESV we found a LV dilation in 129/605 patients (21%). These thresholds were the mean values plus two standard deviations obtained in the control group. 111/129 (86%) were followed up for a mean period of 147.0 months. 83 of 111 (75%) patients had a history of MI and forty three (39%) had undergone surgical revascularizations. During the follow-up, 21 events (5 cardiac deaths, 3 nonfatal MI, 13 late revascularizations) occurred. All post-stress perfusion and functional parameters were more compromised in patients with CE compared with patients without events, but only rest EDV, rest ESV, post-stress ESV and WT-SSS reached statistical significance (201 ml vs 176 ml; p=0.035; 137 ml vs 113 ml; p=0.047; 143 ml vs 117 ml; p=0.034, 19 vs 15; p=0.048, respectively). Multivariate Cox proportional analysis demonstrated that stress ESV added significantly prognostic information over WT-SSS in predicting CE (p=0.046). CONCLUSIONS: Stress ESV has incremental prognostic value compared with wall thickening in predicting CE, in CAD patients with dilated cardiomyopathy. Perfusion parameters failed to show prognostic information in these patients.

Adult↗

Clinical impact of echocardiography in prognostic stratification after acute myocardial infarction.

Risk stratification is mandatory in the management of the postinfarction period. The identification of high-risk patients, on the basis of clinical data (recurrent angina, overt heart failure, etc.), is quite easy, whereas stratification of uncomplicated subjects needs an accurate noninvasive strategy. In the last 20 years, echocardiography has been gaining an increasing role, allowing increasingly precise evaluation of infarct size. This detection of the extent of infarct size has a definite prognostic value. Since 1980, we have observed that a dysfunctioning left ventricular myocardium >40% marked patients with a poor prognosis. These observations are most important in asymptomatic infarct patients, in whom clinical features may not reflect the amount of left ventricular dysfunction. Our recent results on a large series of patients with acute myocardial infarction (MI) without overt heart failure have shown that the extension of wall motion abnormalities at 2-dimensional (2D) echocardiography was highly predictive of cardiac death or new coronary events in a 3-year follow-up (univariate analysis; p <0.0005). Echocardiography also plays an important role in detecting postinfarct ischemia, as seen by its wide use during stress tests. In our experience, the response to exercise echocardiographic testing has a high prognostic value. In fact, in our series, univariate analysis (Kaplan-Meier) showed that the best predictors of coronary events were the number of markers of ischemia during exercise (p <0.00001), the work load (p <0.00001), a positive exercise echo (p <0.0005), and the echo score at rest (p <0.0005). Multivariate analysis (Cox) confirmed these data: number of markers of ischemia: odds ratio (OR) 4.45, 95% confidence interval (CI) 1.5-13.1; work load: OR 2.46, CI 1.3-4.5; positive exercise echo OR 1.88, CI 1.1-3.2. Thus, serial echocardiography together with predischarge stress echocardiography is recommended for risk stratification after acute MI. In particular, in thrombolytic-treated patients, echo examinations allow the detection of functional recovery of viable reperfused myocardium whereas stress echo may show exercise-induced worsening in the region supplied by the infarct-related vessel, a predictor of a higher rate of coronary events.

Echocardiography, Doppler↗

Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery.

UNLABELLED: Predicting outcome after aggressive therapy for advanced rectal cancer remains difficult. (18)F-FDG PET has emerged as a valid method for predicting patient outcomes after therapy in an increasing number of cancers. We evaluated the prognostic information obtained from the degree of change in tumor (18)F-FDG PET uptake induced by chemoradiation before radical curative surgery in patients with T3/T4 rectal cancer. METHODS: The study included 34 consecutive patients with T3/T4 Nx M0 rectal cancer on structural imaging, who underwent staging and postchemoradiation (18)F-FDG PET before planned curative surgery. Change in (18)F-FDG uptake was graded visually as complete (CMR), partial (PMR), or no (NoMR) metabolic response. Pre- and postchemoradiation (18)F-FDG PET-derived standardized uptake values (SUVs) were then obtained for PMR patients to determine whether SUV further stratified this subgroup. Operative findings were available in 30 patients (3 excluded because of (18)F-FDG PET-defined M1 disease, 1 refused surgery). Clinical status at study closeout (alive free from disease, FFD; alive with disease, AWD; or died of disease, DOD) was available for all patients. RESULTS: A pathologic complete response was found in only 6 of 30 patients (5 CMR, 1 false-positive PMR). However, after an estimated median 3.1 y of follow-up, all 17 CMR patients were FFD, 6 of 10 PMR patients were FFD, 2 of 10 had DOD, and 2 of 10 were AWD. All 3 NoMR patients DOD. PET response was highly significantly associated with overall survival duration (P < 0.0001) and time to progression (P < 0.0001). Pathologic complete response was the only other statistically significant prognostic factor (P < 0.03). The percentage of maximum SUV change after chemoradiation was not predictive of survival in PMR patients. CONCLUSION: Using a simple qualitative assessment, postchemoradiation (18)F-FDG PET scintigraphy provides good medium-term prognostic information in patients with advanced rectal cancer undergoing radical surgery with curative intent.

Adult↗

Kynurenine metabolism-related gene signature for prognostic stratification in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden with high mortality rates and limited therapeutic options. The identification of reliable biomarkers for early diagnosis and prognosis prediction is urgently needed. Kynurenine metabolism, a critical pathway in immune regulation and tumor progression, has been implicated in various cancers. However, its prognostic value in HCC has not been fully elucidated. This study aimed to develop a prognostic risk model based on kynurenine metabolism-related genes (KMRGs) for HCC patients. METHODS: Transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. Survival analysis and functional enrichment analysis were conducted to validate the predictive performance of the model and to investigate the underlying mechanisms. ALDH8A1 was ultimately identified as a target gene based on survival analysis, and its impact on tumor cell migration was assessed using the HCC cell line. RESULTS: A prognostic model based on seven KMRGs was established. The high-risk group exhibited significantly worse overall survival compared to the low-risk group. Functional enrichment analysis in high-risk patients highlighted significant enrichment in core biological processes, including spliceosome assembly and ribonucleoprotein complex biogenesis. Furthermore, a nomogram integrating the risk score and clinical pathological features was developed, demonstrating moderate predictive performance for HCC prognosis. CONCLUSIONS: This study successfully constructed a prognostic risk model based on seven KMRGs, providing a valuable tool for predicting clinical outcomes in HCC patients. These findings highlight the potential role of kynurenine metabolism in HCC progression and offer new insights for future therapeutic strategies.

ALDH8A1↗

Identification of a novel signature for prognostic stratification and integrative analyses in lung adenocarcinoma.

BACKGROUND: Recently, research has revealed that the Golgi apparatus is involved in the development process of cancer; however, the specific effect of Golgi apparatus-related genes (GAGs) in lung adenocarcinoma (LUAD) remains unclear. This study aims to construct a more concise and practical risk model in LUAD using GAG. METHODS: The gene expression profiles of patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and GAGs were downloaded from the Gene Set Enrichment Analysis (GSEA) database. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were performed to identify the prognostic GAG signature. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. The correlation between the risk model and the immune landscape was examined using CIBERSORT and TIDE analyses. Also, the genes in the signature were assessed by single-cell RNA sequencing (scRNA-seq). RESULTS: A prognostic signature comprising 5 GAG genes (GNPNAT1, RGS20, CAV3, NTSR1, and FURIN) was established after LASSO and multi-Cox analyses. Both the Kaplan-Meier analysis and the ROC curves supported the strong predictive utility of the risk model. Specifically, the former yielded significant stratification in all three validation datasets (P=1.2001e-05, P=0.006, and P=0.04), while the latter provided further evidence of its predictive precision through the area under the curve. In addition, we found that the low-risk group responded better to immunotherapy than the high-risk group (P<0.0001). scRNA-seq analysis revealed the distribution patterns of the 5 GAG genes in cells. Finally, we assessed the situation of tumor mutation burden (TMB) and performed functional analysis based on the risk model of GAGs. CONCLUSIONS: The risk model based on GAGs can effectively stratify the prognosis of patients and predict immunotherapy responses in LUAD.

Golgi apparatus↗

Prognostic stratification of patients after myocardial infarction.

An attempt was made to stratify risk of subsequent cardiac events in post-infarct patients according to a combination of the results of clinical assessment, routine diagnostic investigations, and pre-discharge exercise testing in 350 consecutive patients who were followed up for one year. Patients were classified prospectively on the basis of the extent of myocardial damage as assessed by peak enzyme release, reciprocal change on the electrocardiogram at the time of myocardial infarction, Norris prognostic index, ability to perform a pre-discharge exercise test (and test result), and ability to tolerate beta adrenergic blockade on discharge. Of the 50 patients with contraindications to pre-discharge exercise testing, 26% died or had reinfarctions compared with 9% of the 300 exercised patients; the 24 non-exercised patients with evidence of extensive myocardial damage or reciprocal changes on the electrocardiogram were particularly at risk. Similarly, among the 300 exercised patients, extensive myocardial damage, reciprocal change on the electrocardiogram, and ST depression on exercise testing were the major risk markers in that each identified at least 75% of the patients who had subsequent cardiac events. The 63 exercised patients who had all three of these major risk markers constituted a high risk group: 18 (29%) died or had reinfarction. Of the remaining 237 patients, only 9 (4%) had cardiac events. The 35 high risk patients with exercise induced angina pectoris or clinical contraindications to beta blockade were particularly at risk; 15 (43%) died or had reinfarction. This approach to risk stratification identified a small cohort of high risk patients in a large population of myocardial infarction survivors; it also identified a large group with a very low risk of subsequent cardiac events.

Electrocardiography↗

Prognostic stratification of Dukes B colon cancer by a neoglycoprotein.

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.

Biomarkers, Tumor↗

Immune-Like Malignant Epithelial Programs Shape Tumor-Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single-cell RNA-sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy-number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell-cell communication profiling. Single-cell-derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning-based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune-like state associated with genomic instability, immune-related transcriptional activity, tumor-immune communication, and patient outcomes. The resulting immune-like malignant epithelial cell signature (IMEC-Sig) consistently stratified survival across multiple cohorts. Low IMEC-Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan-cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC-Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.

Humans↗

Prognostic stratification of patients with anaplastic gliomas according to genetic profile.

BACKGROUND: There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival. METHODS: The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression. RESULTS: The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas. CONCLUSIONS: The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.

Adult↗

Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. METHODS: The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. RESULTS: The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. CONCLUSIONS: Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.

Acute Kidney Injury↗

FDG-PET status following chemoradiotherapy provides high management impact and powerful prognostic stratification in oesophageal cancer.

PURPOSE: The purpose of this study was to evaluate the impact of FDG-PET following chemoradiotherapy (CRT) on treatment planning and survival in patients with oesophageal cancer (OC). METHODS: Fifty-three consecutive OC patients had a post-treatment PET scan to evaluate tumour response to CRT prior to possible surgery. Baseline pre-CRT PET was performed in 33 patients. Prospectively recorded post-CRT management plans were compared with post-PET treatment. High impact was defined as a change in treatment intent or modality. Survival was analysed using the Kaplan-Meier product limit method and Cox proportional hazards regression model. RESULTS: After completion of CRT, 23/53 patients (43%) achieved complete metabolic response (CMR), as compared with only four (8%) with complete response on computed tomography. High PET impact was observed in 19 patients (36%). CMR was strongly predictive of survival (p<0.008) on multivariate analysis. CMR patients in whom resection was not performed had comparable survival to those (CMR and non-CMR) who underwent resection. CONCLUSION: The use of post-treatment FDG-PET for assessment of tumour response after CRT changed the clinical management of more than one-third of OC patients. CMR status as assessed by PET powerfully stratified prognosis. Even in the absence of a baseline study, normalisation of uptake at all sites of known tumoral involvement carries a good medium-term prognosis.

Adult↗

Microarray studies of prognostic stratification and transformation of follicular lymphomas.

Follicular lymphoma (FL) is a common, indolent malignancy with a natural history of transformation to the more aggressive form of diffuse large B-cell lymphoma (DLBCL) in 25-60% of cases. In order to understand the pathogenesis of lymphoma genesis and evolution, the molecular changes characteristic of FL and transformed DLBCL are being studied. The most common abnormality associated with FL is the t(14;18)(q32;q21) chromosomal translocation, but many more molecular aberrations have been found in patient subgroups. The study of gene expression profiling using DNA microarrays enables large scale, comparative analyses of gene expression. Its implementation in the research on FL has led to advances in disease diagnosis and classification and has the potential to lead to pathogenesis-based individualised therapies.

Cell Transformation, Neoplastic↗