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BACKGROUND: The metabolic environment of glioma is extremely complex. Pyrimidine metabolism can significantly influence malignant progression of multiple kinds of cancer cells. In this study, we intend to explore the relationship between pyrimidine metabolism and malignant progression of glioma. METHODS: We analyzed two glioma RNA-sequencing databases to construct a pyrimidine metabolism-related risk signature. An individualized prognosis prediction model based on this risk signature was established. Functional analysis and in vitro experiments were conducted to assess the role of pyrimidine metabolism in the tumor-immune microenvironment and malignant progress of gliomas. RESULTS: The high-risk group, as predicted by the pyrimidine metabolism-related risk score, showed a tendency toward more malignant entities and poorer survival outcomes. Functional analysis revealed that pyrimidine metabolism significantly regulates the tumor-immune microenvironment. In vitro experiments confirmed that targeting pyrimidine metabolism-related genes can inhibit malignancy of glioma cell. CONCLUSION: In short, the pyrimidine metabolism-related signature we established could serve as an independent prognostic biomarker in diffuse gliomas and has a close association with regulation of the tumor-immune microenvironment.
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The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.
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Predisposição Genética para Doença , Neuroblastoma , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/sangue , Neuroblastoma/genética , Neuroblastoma/sangue , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Masculino , Feminino , México , Pré-Escolar , Lactente , Criança , Prognóstico , Genótipo , Estudos de Coortes , Estudos de Casos e ControlesRESUMO
BACKGROUND: Endometrial cancer (UCEC) is one of the most common malignant tumors in gynecology, and early diagnosis is crucial for its treatment. Currently, there is a lack of early screening tests specific to UCEC, and treatment advances are limited. It is crucial to identify more sensitive biomarkers for screening, diagnosis, and predicting UCEC. Previous studies have shown that UBE2T is involved in the development of various tumors such as breast cancer and liver cancer, but research on the role of UBE2T in UCEC is limited. METHODS: Using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and UALCAN databases, we analyzed the differential expression of UBE2T mRNA and protein in endometrial cancer (UCEC), along with its clinical relevance. A total of 113 clinical samples were collected, and immunohistochemistry and Western blot analysis were employed to validate bioinformatics analysis results. Volcano plots were generated using UBE2T and its differentially expressed genes, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and immune infiltration analysis were used to predict the functional role of UBE2T in UCEC progression. Correlation between UBE2T expression and patient survival was analyzed using TCGA data, and Kaplan-Meier survival curves were plotted. RESULTS: UBE2T is significantly overexpressed in UCEC and correlates with poor prognosis. Its overexpression is closely associated with mitosis, cell cycle regulation, and histological grade in UCEC patients. CONCLUSION: UBE2T is highly expressed in UCEC and suppresses anti-tumor immune responses in UCEC patients. It serves as a key participant in UCEC progression, associated with a range of adverse outcomes, and holds potential as a clinical diagnostic and prognostic biomarker.
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Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.
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The determination of the cancer prognosis is paramount for patients and medical personnel so that they can devise treatment strategies. Transcriptional-based signatures and subtypes derived from cancer biopsy material have been used in clinical practice for several cancer types to aid in setting the patient prognosis and forming treatment strategies. Other genomic features in cancer biopsies, such as copy number alterations (CNAs), have been underused in clinical practice, and yet they represent a complementary source of molecular information that can add detail to the prognosis, which is supported by recent work in breast, ovarian, and lung cancers. Here, through a systematic strategy, we explored the prognostic power of CNAs in 37 cancer types. In this analysis, we defined two modes of informative features, deep and soft, depending on the number of alleles gained or lost. These informative modes were grouped by amplifications or deletions to form four single-data prognostic models. Finally, the single-data models were summed or combined to generate four additional multidata prognostic models. First, we show that the modes of features are cancer-type dependent, where deep alterations generate better models. Nevertheless, some cancers require soft alterations to generate a feasible model due to the lack of significant deep alterations. Then, we show that the models generated by summing coefficients from amplifications and deletions appear to be more practical for many but not all cancer types. We show that the CNA-derived risk group is independent of other clinical factors. Furthermore, overall, we show that CNA-derived models can define clinically relevant risk groups in 33 of the 37 (90%) cancer types analyzed. Our study highlights the use of CNAs as biomarkers that are potentially clinically relevant to survival in cancer patients.
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Variações do Número de Cópias de DNA , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia , Prognóstico , Biomarcadores Tumorais/genéticaRESUMO
Abstract Objective Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. Method A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. Results Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. Conclusion The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.
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INTRODUCTION: The somatostatin analogs (SSA) octreotide and lanreotide are a mainstay in the treatment of neuroendocrine tumors (NET). The two pivotal trials differed considerably in terms of patient characteristics and are not directly comparable. Further comparative data are lacking. METHODS: This retrospective chart review study included patients with gastroenteropancreatic NET grade 1 or 2 who were treated with octreotide LAR or lanreotide autogel. The main aim was to compare the two SSA based on progression-free survival (PFS) and overall survival (OS) from treatment start. RESULTS: In total, 129 patients were analyzed, 60% (n = 77) had a small intestinal NET and 31% (n = 40) a pancreatic NET. Histologically, 34% (n = 44) had NET G1, 55% (n = 71) a NET G2, and 11% (n = 14) a NET G1/G2 unclassified. Lanreotide was used in 90 patients (70%) and octreotide in 39 patients (30%). Overall, the median PFS was 32.2 months (95% CI 23.0-42.9 months). No PFS difference (p = 0.8) was observed between lanreotide (29.8 months, 95% CI 18.7-48.5 months) and octreotide (36.0 months, 95% CI 23.2-68.2 months). Median OS from treatment start was calculated at 93.5 months (95% CI 71.1-132.9 months). Again, the median OS following lanreotide (113.4 months, 95% CI 62.3-NA months) or after octreotide (90.3 months, 95% CI 71.1-NA months) did not differ significantly (p > 0.9). CONCLUSIONS: Our long-term experience with octreotide and lanreotide in NET did not reveal differences in antitumor effectiveness. This is consistent with previous reports and might suggest that both SSA can be used interchangeably if needed.
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PURPOSE: This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil. MATERIALS AND METHODS: HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors. RESULTS: A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence. CONCLUSION: In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.
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Background: The lactate/pyruvate (LP) ratio has been studied as an alternative to serum lactate to determine clinical prognosis. Despite its clinical utility, there is a paucity of evidence evaluating the role of the L/P ratio in patients with sepsis. Methods: We assessed the clinical utility of the L/P ratio in patients with sepsis. The L/P ratio was measured at baseline, 4 and 8 h after admission. Our primary outcome was to determine the prognostic utility of the L/P ratio on the 15-day mortality risk. Our secondary outcomes were to compare the L/P ratio across time and its prognostic utility against standard risk calculators such as APACHE-II and SOFA scores. Results: We had a total of 80 patients, with 18 (22.5%) survivors and 62 (77.5%) non-survivors. While we found that patients having higher L/P ratios at 8 h had an increased 30-mortality risk (OR 1.08, 95% CI 1.02-1.18), the model's performance showed no difference when compared to other measurements of the L/P ratio that showed no association with mortality (p-value: 0.45). For our secondary outcome, we found that the APACHE-II and SOFA scores have better performance and predictability than the L/P ratio (AUC 0.83 and AUC 0.80, respectively), but showed no association with mortality (OR 1.07, 95% CI 1.01-1.17 and OR 1.08, 95% CI 1.02-1.18). Conclusions: Based on our findings, the L/P ratio appears to function more effectively as an early predictor of mortality when used as an adjuvant biomarker with other clinical parameters.
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Infective endocarditis (IE) associated with implantable cardiac devices (ICD) is a serious disease with high mortality rates. The increased number of ICD implants has led to increased ICD infection rates. The aim of this study was to characterize clinical, laboratory profiles and the prognosis of cardiac-device-related endocarditis (CDIE), as well as to identify predictors of in-hospital death. A total of 274 patients with IE were included in a prospective cohort (2007-2019). From these, 82 patients (30%) had CDIE (46 pacemakers, 23 cardioverter defibrillators, and 13 cardiac resynchronization therapy devices). Predisposed conditions; clinical, laboratory and echocardiographic parameters; etiologic agents; and in-hospital outcomes were evaluated. The mean age was 55.8 ± 16.4 years, where 64.6% were male. Among the clinical manifestations at diagnosis, the most prevalent were heart failure (67.9%), fever (60.5%), anorexia/hyporexia (44.4%), and heart murmur (37.5%). The median serum C-reactive protein (CRP) level at diagnosis was 63 mg/L (interquartile range [IQR] 20-161). Etiological agents were identified through positive blood cultures in 55% of cases. The main etiologic agents were negative-coagulase staphylococci (19.5%) and Staphylococcus aureus (18.3%). Vegetation was identified in 74 patients (90.1%). In-hospital mortality was 28%. CRP concentrations at diagnosis were identified as markers of disease severity (odds ratio [OR] 1.006; 95%CI 1.001-1.011; p = 0.016), and the worsening of heart failure was associated with unfavorable outcomes (OR 3.105; 95%CI 1.397-6.902; p = 0.005). Unlike what is traditionally accepted, CDIE does not have a better prognosis.
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OBJECTIVE: The aim of this study was to construct a prognostic model based on the TP53 mutation to calculate prognostic risk scores of patients with HPSCC. METHODS: TP53 mutation and transcriptome data were downloaded from the TCGA databases. Gene expression data from GSE65858, GSE41613, GSE3292, GSE31056, GSE39366, and GSE227156 datasets were downloaded from the GEO database. GSEA, univariate, multivariate Cox analyses, and LASSO analysis were employed to identify key genes and construct the prognostic model. ROC curves were utilized to validate the OS and RFS results obtained from the model. The associations between risk scores with various clinicopathological characteristics and immune scores were analyzed via ggplot2, corrplot package, and GSVA, respectively. Single-cell sequencing data was analyzed via unbiased clustering and SingleR cell annotations. RESULTS: Initially, two key genes, POLD2 and POLR2G, were identified and utilized to construct the prognostic model. Samples were divided into different risk groups via the risk scores obtained from the model, with high-risk group samples exhibiting poorer prognosis. Furthermore, the risk score exhibited a positive correlation with lymphatic metastasis in patients and the immune scores of CD4+ T, CD8+ T, dendritic cell, macrophage, and neutrophil. The immune responses also exhibited notable disparities between the high- and low-risk groups. The results of single-cell sequencing analysis demonstrated that epithelial cells and macrophages were relatively abundant in HPSCC samples. POLD2 and POLR2G exhibited higher expressions in epithelial cells, with most of the identified pathways also enriched in epithelial cells. CONCLUSION: The prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model. LEVEL OF EVIDENCE: Level 5.
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INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. PATIENTS AND METHODS: Patients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan-Meier survival analysis and COX regression analysis. RESULTS: Among 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94-15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51-15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56-23.18) were independent predictors of adverse outcomes. CONCLUSIONS: CSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.
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Background/Objectives: Increasing evidence indicates that body composition can significantly influence prognosis in women with breast cancer. However, alterations in body composition, particularly among young women (<40 years), remain largely unknown and underexplored. This study aimed to investigate the relationship of computed tomography (CT)-derived body composition with mortality rates among young women recently diagnosed with breast cancer, identifying the best-correlated cutoff value. Methods: This is a bi-set cohort study with retrospective data collection. Women newly diagnosed with ductal invasive breast cancer, aged 20 to 40 years, treated in reference oncology units were included. Body composition was assessed using CT scans at the third lumbar vertebra (L3) level, including muscle and adipose compartments. The outcome of interest was the incidence of overall mortality. A maximally selected log-rank Cox-derived analysis was employed to assess the cutoffs associated with mortality. Results: A total of 192 women were included before any form of treatment (median age of 35 years, IQ range: 31-37). Overall mortality occurred in 12% of the females. Stages III-IV were the most frequent (69.5%). Patients who died had a significantly lower muscle area index. CT-derived muscle area was inversely associated with mortality. Each 1 cm2/m2 decrease in skeletal muscle index increased the mortality hazard by 9%. Higher values of adiposity compartments were independently associated with higher mortality. Conclusions: Our study highlights the predictive significance of skeletal muscle area and adipose tissue in predicting survival among young women recently diagnosed with breast cancer.
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Composição Corporal , Neoplasias da Mama , Tomografia Computadorizada por Raios X , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/diagnóstico por imagem , Adulto , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Adulto Jovem , Músculo Esquelético/diagnóstico por imagem , Fatores de Risco , Prognóstico , Adiposidade , Estudos de CoortesRESUMO
Since the first presentation at the IV Iberoamerican Academy of Neuropediatrics Congress in 1995, our group has studied self-limited infantile epilepsy (SeLIE), both familial and non-familial, corroborating that they belong to the same entity due to their clinical and electroencephalographic characteristics and excellent prognosis. Associations were found with paroxysmal dyskinesias and migraine, as well as with hemiplegic migraine, episodic ataxia and intellectual disability in atypical cases. Mutations in PRRT2 are the main cause of SeLIE, however, other genes, such as SCN2A, KCNQ2-3 and SCN8A, have been recognized. Drugs for focal seizures that act on sodium channels are indicated. In emergencies, during cluster seizures, the use of benzodiazepines is important. In this publication, we review our contribution in SeLIE from our first report to the present and review the existing literature on the subject.
Desde la primera presentación en el IV Congreso de la Academia Iberoamericana de Neurología Pediátrica en 1995, nuestro grupo ha estudiado las epilepsias autolimitadas del lactante (EAL), tanto familiares y no familiares, corroborando que pertenecen a una misma entidad por sus características clínicas, electroencefalográficas y excelente pronóstico. Se encontraron asociaciones con discinesias paroxísticas y migraña, como también con la migraña hemipléjica, la ataxia episódica y la discapacidad intelectual en casos atípicas. Las mutaciones en PRRT2 son la principal causa de EAL. Sin embargo, otros genes, como SCN2A, KCNQ2-3 y SCN8A, han sido reconocidos. Los fármacos para las crisis focales que actúan sobre los canales de sodio son los indicados. En emergencias, durante las convulsiones agrupadas, es importante el uso de benzodiacepinas. En esta publicación, hacemos un recorrido de nuestro aporte en EAL desde nuestra primera contribución hasta la actualidad y además realizamos una revisión de la literatura existente sobre el tema.
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Epilepsia , Humanos , Lactente , Epilepsia/genética , Academias e Institutos , Eletroencefalografia , Mutação , Proteínas do Tecido Nervoso/genética , Congressos como Assunto , Proteínas de MembranaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors, exhibiting a high morbidity and mortality rate. The mechanism of its occurrence and development requires further study. The objective of this study was to investigate the role of SERPINA12 in the diagnosis, prognosis prediction and biological function within HCC. METHODS: The Cancer Genome Atlas (TCGA) data were employed to analyze the relationship between clinical features and SERPINA12 expression in HCC. Kaplan-Meier curves were utilized to analyze the correlation between SERPINA12 expression and prognosis in HCC. The function of SERPINA12 was determined by enrichment analysis, and the relationship between SERPINA12 expression and immune cell infiltration was investigated. The expression of SERPINA12 was examined in 75 patients with HCC using RT-qPCR and immunohistochemistry, and survival analysis was performed. RESULTS: The expression of SERPINA12 from TCGA database was found to be significantly higher in HCC tissues than in normal tissues and carried a poor prognosis. ROC curve demonstrated the diagnostic potential of SERPINA12 for HCC. The multivariate Cox regression analysis showed that pathologic T stage, tumor status, and SERPINA12 expression were independently associated with patient survival. The SERPINA12 expression was found to correlate with immune cell infiltration. Our RT-qPCR and immunohistochemical analysis revealed high expression of SERPINA12 in tumor tissues. Survival analysis indicated its association with poor prognosis. CONCLUSION: SERPINA12 is a promising biomarker for diagnosis and prognosis, and it is associated with immune cell infiltration.
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INTRODUCTION: Triple-negative breast cancer (TNBC) is one of the most aggressive cancers in women, therefore it is necessary to determine novel prognostic markers to estimate survival and advancement the treatment of the disease. Recently, PCMT1, a protein mediating TNBC immune infiltration, has gained attention as a potential therapeutic target. The aim of the study was to demonstrate the relationship between PCMT1 protein overexpression as a prognostic indicator for patients with TNBC cancer and patient survival. MATERIALS AND METHODS: The study included 64 samples collected from 64 TNBC patients. We used the ImageJ software with the IHC Profiler driver for image analysis. To improve the reliability of the results, we expanded the analysis by including The Cancer Genome Atlas cohort. RESULTS: We observed strong PCMT1 immunoreactivity in breast cancer samples and PCMT1 expression in TNBC was significantly higher than in the control group. Patients with high PCMT1 expression had a significantly lower overall survival rate (60.62% vs. 90.35%, respectively) than patients with low PCMT1 expression. In our study and TCGA groups, PCMT1 expression did not correlate with lymph node involvement and distant metastases but correlated with tumor stage. The results obtained in a larger TCGA group are consistent with those in our research group. Overexpression of PCMT1 was a prognostic marker of shorter survival in patients with TNBC. CONCLUSIONS: The overexpression of the PCMT1 protein in triple negative breast cancer significantly correlated with shorter overall survival. The confirmed association could be a potential prognostic biomarker for patients with TNBC.
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PURPOSE: The objective of this study is to assess the prognostic efficacy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET-CT) parameters in nasopharyngeal carcinoma (NPC) and identify the best machine learning (ML) prognostic model for NPC patients based on these 18F-FDG PET/CT parameters and clinical variables. METHOD: A cohort of 678 patients diagnosed with NPC between 2016 and 2020 was analyzed in this study. The model was constructed using four advanced ML algorithms, namely Random Forest (RF), Extreme Gradient Boosting (XGBoost), Least Absolute Shrinkage and Selection Operator (LASSO), and multifactor COX step-up regression. Statistical significance of the models was assessed using Kaplan-Meier (K-M) curves, with a significance level established at P < 0.05. The prognostic efficacy of the models was evaluated through the analysis of receiver operating characteristic (ROC) curves, with the area under the ROC curve (AUC) serving as a criterion for model selection. The decision curve analysis (DCA) and concordance index (C-index) were employed to assess the precision of the optimal model. RESULTS: Multivariate analysis revealed age, T stage, and metabolic tumor volume (MTV) for the primary nasopharyngeal tumor (MTVT) as significant independent prognostic factors for overall survival (OS) in NPC patients. Additionally, the LASSO model identified six key variables, including peak standardized uptake value (SUV-peak) for the primary nasopharyngeal tumor (SUV-peak(T)), MTVT, heterogeneity index for neck lymph nodes (HIN), age, pathological type, and T stage. Remarkably, the LASSO model demonstrated superior performance with a 5-year AUC of 0.849 compared to other models. Further assessment using the C-index and DCA confirmed the accuracy of the LASSO model. Subgroup analysis revealed notable risk factors, such as a high heterogeneity index (HI) for the primary nasopharyngeal tumor (HIT), MTV values for neck lymph nodes (MTVN), and HIN. CONCLUSIONS: We developed a novel prognostic machine learning model that integrates 18F-FDG PET-CT parameters and clinical characteristics, significantly enhancing prognosis prediction in NPC.
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OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.
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Objective: This study aimed to assess the prognostic value of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) in predicting mortality and characterizing disease progression patterns in ALS patients in Colombia. Methods: We conducted a retrospective longitudinal analysis of 537 ALS patients from the Roosevelt Institute Rehabilitation Service between October 2008 and October 2022. The study excluded nine patients due to incomplete data, resulting in 528 individuals in the analysis. ALS diagnoses were confirmed using the revised El Escorial and Gold Coast criteria. Disease progression was assessed using the ALSFRS-R, and mortality data were sourced from follow-up calls and a national database. Statistical analysis included Cox proportional hazards models to identify mortality predictors and Growth Mixture Modeling (GMM) to explore ALS progression trajectories. Results: The majority of the cohort (63.8%) deceased within the 84-month follow-up period. Survival analysis revealed that each point increase in the ALSFRS-R rate was associated with a 2.22-fold (95% CI =1.99-2.48, p < 0.001) increased risk of mortality. In the population with data from two clinical visits, the ALSFRS-R rate based on initial assessments predicted mortality more effectively over 36 months than the rate based on two evaluations. GMM identified three distinct progression trajectories: slow, intermediate, and rapid decliners. Conclusions: The ALSFRS-R rate, derived from self-reported symptom onset, significantly predicts mortality, underscoring its value in clinical assessments. This study highlights the heterogeneity in disease progression among Colombian ALS patients, indicating the necessity for personalized treatment approaches based on individual progression trajectories. Further studies are needed to refine these predictive models and improve patient management and outcomes.