scholarly journals Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5237
Author(s):  
Carmen Salguero-Aranda ◽  
Paula Martínez-Reguera ◽  
David Marcilla ◽  
Enrique de Álava ◽  
Juan Díaz-Martín
Keyword(s):  
Prognostic Value ◽  
Gene Fusion ◽  
Fatal Outcome ◽  
Case Series ◽  
Tumor Location ◽  
P53 Mutation ◽  
Clinicopathological Parameters ◽  
Late Relapse ◽  
Biological Knowledge ◽  
Molecular Alterations

Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location.

Comprehensive analysis integrating both clinicopathological and gene expression data in more than 1,500 samples: Proliferation captured by gene expression grade index appears to be the strongest prognostic factor in breast cancer (BC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
C. Sotiriou ◽  
P. Wirapati ◽  
S. Loi ◽  
B. Haibe-Kains ◽  
C. Desmedt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Outcome ◽  
Gene Expression Data ◽  
Prognostic Value ◽  
Expression Patterns ◽  
P53 Mutation ◽  
Comprehensive Analysis ◽  
Biological Factor ◽  
Biological Knowledge ◽  
Expression Data

507 Background: Although, the development of high-throughput gene expression technologies has allowed the identification of several “molecular signatures” predicting clinical outcome, no attempt has been made yet to perform a comprehensive analysis integrating both clinicopathological, and gene expression data. Here, we aim to elucidate the relationship between clinical parameters and tumor markers, with gene expression patterns and their interaction with prognosis. Methods: We analyzed gene expression and clinical data from several published studies, including more than 1500 BC patients. We developed several gene expression indices associated with different biological stages of disease characterized by the expression of hormone receptors, HER2 amplification, p53 mutation, angiogenesis, tumor invasion and proliferation. Multivariable analyses were used to characterize the dependency patterns between these indices and their impact on survival. Results: Estrogen receptor (ER) and HER2 indices were the most prominent discriminators dichotomizing tumor samples into two main subsets in agreement with the previously proposed BC subtypes. Tumor proliferation, assessed by our previously reported gene expression index (GGI), was the most strongly associated with prognosis (HR 2.29, CI 1.88–2.78, p<0.0001). Almost all ER- and HER2+ tumors were associated with high GGI scores. In contrast, ER+ and HER2- tumors showed a whole range of GGI values. Within the high proliferation subset, ER- and HER2+ indices did not have any prognostic value. Similar results were found with relation to p53 mutation index. Nodal status and tumor size, which essentially measure the duration of disease, retained prognostic value in addition to proliferation. Conclusions: Proliferation captured by the GGI appears to be a key biological factor, downstream of ER, HER2 and p53. Although understanding the upstream factors is important for advancing biological knowledge and therapeutic interventions, GGI seems to be the most important factor predicting clinical outcome in BC and deserves consideration as stratification factor in clinical trials. No significant financial relationships to disclose.

Predictive and prognostic biomarkers with therapeutic targets in colorectal cancer: A 2021 update on current development, evidence, and recommendation

2021 ◽  
pp. 107815522110055
Author(s):  
Clement Chung
Keyword(s):  
Checkpoint Inhibitors ◽  
Therapeutic Targets ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Tumor Location ◽  
Prognostic Biomarkers ◽  
Her2 Gene ◽  
Braf Mutations ◽  
Therapeutic Implications ◽  
Molecular Alterations

Although therapeutically actionable molecular alterations are widely distributed across many cancer types, only a handful of them show evidence of clinical utility and are recommended for routine clinical practice in the management of cancers of colon and rectum (CRC). This 2021 update aims to provide a succinct summary on the use of prognostic and/or predictive biomarkers (expanded RAS, BRAF, microsatellite-high [MSI-H] or deficient mismatch repair [dMMR], neurotrophic tyrosine receptor kinase [ NTRK] fusion genes, and human epidermal growth factor receptor type II [ HER2] gene amplification) associated with CRC. Therapeutic implications of each relevant predictive or prognostic biomarker for patients with CRC are described, along with discussion on new developments on (1) biomarker-driven therapies such as testing of BRAF, MLH1 promoter methylation and MMR germline genes in differentiating sporadic CRC or hereditary conditions such as Lynch syndrome; (2) first-line use of immune checkpoint inhibitors in metastatic CRC; (3) risk stratification and therapy selection based on primary tumor location (left-sided vs. right-sided colon cancer); (3) atypical BRAF mutations; (4) use of EGFR directed therapy in the perioperative oligometastatic disease setting; (5) re-challenge of EGFR directed therapy and (6) personalizing therapy of fluoropyrimidine and irinotecan based on new evidence in pharmacogenomic testing. Data are collected and analyzed from available systematic reviews and meta-analyses of treatments with known therapeutic targets in CRC, which may be associated with predictive and/or prognostic biomarkers. Discussions are presented in an application-based format, with goal to empower pharmacists or other clinicians to gain awareness and understanding in biomarker-driven cancer therapy issues.

scholarly journals Prognostic Value of Liver and Spleen Stiffness in Patients with Fontan Associated Liver Disease (FALD): A Case Series with Histopathologic Comparison

2021 ◽  
Vol 8 (3) ◽  
pp. 30
Author(s):  
Massimo Padalino ◽  
Liliana Chemello ◽  
Luisa Cavalletto ◽  
Annalisa Angelini ◽  
Marny Fedrigo
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Prognostic Value ◽  
Fontan Operation ◽  
Vena Cava ◽  
Case Series ◽  
Morbidity And Mortality ◽  
Post Mortem ◽  
Spleen Stiffness

The Fontan operation is the current surgical procedure to treat single-ventricle congenital heart disease, by splitting the systemic and pulmonary circulations and thus permitting lifespan to adulthood for the majority of newborns. However, emerging data are showing that Fontan-associated liver disease (FALD) is an increasing related cause of morbidity and mortality in patients with the Fontan circuit. We described the clinical, laboratory, and transient elastography (TE) findings in a case series of adults with the Fontan circuit, and also correlated data with post-mortem histological features, aimed to define the prognostic value of TE in the staging of FALD. All patients presented signs of a long-standing Fontan failure, characterized by reoperation need, systemic ventricle dysfunction, and FALD stigmata (liver and spleen enlargement, portal vein and inferior vena cava dilation, and abnormal liver function tests). Liver and spleen stiffness (LS and SS) values were indicative of significant liver fibrosis/cirrhosis and the presence of suggestive portal hypertension (LS mean 35.9; range 27.3–44.7 kPa; SS mean 42.1, range 32.2–54.5 kPa). Post-mortem evaluations confirmed a gross hepatic architecture distortion in all cases. All patients died from severe complications related to liver dysfunction and bleeding. TE correlated well with pathological findings and FALD severity. We propose this validated and harmless technique to monitor liver fibrosis extension and portal hypertension over time in Fontan patients, and to identify the optimal timing for surgical reoperations or orthotopic-heart transplantation (OHT), avoiding a higher risk of morbidity and mortality in cases with severe FALD.

scholarly journals In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Zhipeng Zhu ◽  
Jiuhua Xu ◽  
Xiaofang Wu ◽  
Sihao Lin ◽  
Lulu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

scholarly journals Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series

Cases Journal ◽  
2009 ◽  
Vol 2 (0) ◽  
Author(s):  
Aniruddha Ghose ◽  
Abdullah Abu Sayeed ◽  
Amir Hossain ◽  
Ridwanur Rahman ◽  
Abul Faiz ◽  
...  
Keyword(s):  
Barium Carbonate ◽  
Fatal Outcome ◽  
Case Series ◽  
Lessons Learned

COVID-19 situation in Baden-Württemberg, Germany: Preliminary case series study during the first wave

2021 ◽  
Vol 1 (1) ◽  
pp. 6-11
Author(s):  
Dzmitry Katovich ◽  
Claudia Grun ◽  
Hanna Katovich ◽  
Bastian Hauer ◽  
Thomas Iber ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Symptoms ◽  
Fatal Outcome ◽  
Laboratory Data ◽  
Case Series ◽  
Severe Illness ◽  
Case Series Study ◽  
Regional Factors ◽  
Series Study

The present case series study presents the preliminary data of 347 of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positively tested patients in the Mittelbaden hospital, Baden-Baden Bühl, Germany, during the period from March to June 2020. Among the 347 patients, 55% were males. The mean age-wise was 52.5±20.2 years in the overall cohort and 78.9±11.1 years in fatal outcome cases. A total of 120/347 patients (34.6%) required hospitalization, but only 36/347 (10.37%) cases required intensive care. The overall fatality rate was 6.6% (23/347), of which 12 patients were from the intensive care unit. The most frequent clinical symptoms observed were cough (62.5%), hyperthermia (47.8%), rhinorrhea (25.1%), sore throat (23.1%), dyspnea (22.8%), and headache (19.3%). Laboratory data analysis showed no specific findings, but severe laboratory disturbances could predict critical illness. A higher risk of severe illness or lethal outcome in elderly patients with several comorbidities was the most frequent. The fight against COVID-19 infection in Germany seems to be more successful during the first wave than in other countries. The improvement of the healthcare system against infectious outbreaks depends directly on the analysis of regional factors.

Ereptic enzymes and agglutinins in urine in septic diseases and their prognostic value

1934 ◽  
Vol 30 (6) ◽  
pp. 633-633
Author(s):  
Е. Freund ◽  
К. Кadnа
Keyword(s):  
Prognostic Value ◽  
Fatal Outcome ◽  
Definite Relationship

In a study of the agglutination ability and the ability to digest urinary peptone aa. we found a definite relationship between the severity of the case and the amount of enzymes in the urine. Of the 18 cases with no normal agglutinins and ereptic enzymes in the urine, 16 ended fatally, the remaining 2 had a prolonged febrile course. In cases with normal enzymes there was no fatal outcome.

H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  
Keyword(s):  
Cox Regression ◽  
Fatal Outcome ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Integrated Analysis ◽  
Prognostic Impact ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

scholarly journals P14.123 Neurological complications related to checkpoints inhibitors

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii98
Author(s):  
I Esparragosa ◽  
R Valenti-Azcarate ◽  
D Moreno-Ajona ◽  
J Gallego Perez de Larraya
Keyword(s):  
Cerebrospinal Fluid ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Oral Prednisone ◽  
Fatal Outcome ◽  
Case Series ◽  
Neurological Complications ◽  
Ovarian Adenocarcinoma ◽  
Inflammatory Myositis ◽  
Oncological Treatment

Abstract BACKGROUND Currently, immunotherapy is part of the therapeutic arsenal for oncological treatment. Indeed, the need for new medications has led to the development of immune checkpoint inhibitors. Despite favourable oncological outcomes, these treatments have been associated with immune-related adverse events. Although infrequent, neurological toxicities have been reported. Early recognition is crucial for improvement of functional outcome and requires a multidisciplinary approach. OBJECTIVE To describe a case series of patients with neurological complications related to checkpoint inhibitors. PATIENTS AND METHODS We identified six oncological patients who presented immunomediated neurological complications, derived from the use of checkpoints inhibitors. Five cases were men. Ages ranged from 58 to 73 years. Nivolumab, alone or combined, was the most commonly associated drug (4/6). Underlying diseases included lung carcinoma (2/6), melanoma (2/6), renal carcinoma (1/6) and ovarian adenocarcinoma (1/6). An acute demyelinating sensory-motor polyneuropathy and an acute axonal sensory polyneuropathy were documented in two and one case, respectively. In these, the cerebrospinal fluid analysis revealed albuminocytologic dissociation. All three cases improved after treatment with intravenous immunoglobulins (0.4 g/Kg a day for five days). The latter and another case were diagnosed of aseptic meningitis after cerebrospinal fluid lymphocytic pleocytosis was found. High fever was also associated with lower extremities areflexia, weakness and ataxia. Methylprednisolone (1g/day for five days) was administered. One case of necrotizing inflammatory myositis with high levels of creatine kinasa, confirmed by muscular biopsy, involving cervical weakness and ptosis, was effectively treated with Methylprednisolone (1g/day for five days) follow by oral prednisone tapering. An anti-Yo related pancerebellar syndrome was the only case with a fatal outcome despite treatment. CONCLUSION The increasingly frequent use of immunotherapy in the treatment of cancer may lead to an increase in neurological complications. These include a broad spectrum of syndromes with peripheral nervous system predominantly susceptible. Early identification of these and appropriate management of drug-related toxicity are required. Immune-modulating therapies are particularly beneficial.

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