Multimodal therapy of glioblastoma (GBM) reveals inter-individual variability in terms of treatment outcome. Here, we examined whether a miRNA signature can be defined for the a priori identification of patients with particularly poor prognosis.FFPE sections from 36 GBM patients along with overall survival follow-up were collected retrospectively and subjected to miRNA signature identification from microarray data. A risk score based on the expression of the signature miRNAs and cox-proportional hazard coefficients was calculated for each patient followed by validation in a matched GBM subset of TCGA. Genes potentially regulated by the signature miRNAs were identified by a correlation approach followed by pathway analysis.A prognostic 4-miRNA signature, independent of MGMT promoter methylation, age, and sex, was identified and a risk score was assigned to each patient that allowed defining two groups significantly differing in prognosis (p-value: 0.0001, median survival: 10.6 months and 15.1 months, hazard ratio = 3.8). The signature was technically validated by qRT-PCR and independently validated in an age- and sex-matched subset of standard-of-care treated patients of the TCGA GBM cohort (n=58). Pathway analysis suggested tumorigenesis-associated processes such as immune response, extracellular matrix organization, axon guidance, signalling by NGF, GPCR and Wnt. Here, we describe the identification and independent validation of a 4-miRNA signature that allows stratification of GBM patients into different prognostic groups in combination with one defined threshold and set of coefficients that could be utilized as diagnostic tool to identify GBM patients for improved and/or alternative treatment approaches.
- The spine journal : official journal of the North American Spine Society
- Published over 2 years ago
Evidence is lacking on the prognosis and prognostic factors for back-related leg pain and sciatica in patients seeing their primary care physicians. This could guide timely appropriate treatment and referral decisions.
Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive. The aims of this study were to analyse the expression of DSCs and to evaluate their clinical application in lung cancer.
: An understanding of the activated protein signaling architecture in non-small-cell lung cancer (NSCLC) is of critical importance to the development of new therapeutic approaches and identification of predictive and prognostic biomarkers for patient stratification.
BACKGROUND: AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored. METHODS: ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions. RESULTS: Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11. CONCLUSIONS: We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.
Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Expression Is an Independent Prognostic Factor in Pediatric Pilocytic and Pilomyxoid Astrocytoma
- Journal of neuropathology and experimental neurology
- Published about 7 years ago
Prognostic factors in pilocytic astrocytomas (PAs) and pilomyxoid astrocytomas (PMAs) include extent of resection, location, and age, but no molecular markers have been established. Insulin-like growth factor 2 mRNA binding protein 3 (IMP3, IGF2BP3) is predictive of an unfavorable prognosis in other tumors, including high-grade astrocytomas, but its role in PA/PMA is unknown. This study aimed to determine the expression and prognostic value of IMP3 in pediatric PA/PMAs. Insulin-like growth factor 2 mRNA binding protein 3 protein expression was examined by immunohistochemistry in 77 pediatric PAs (n = 70) and PMAs (n = 7) and scored on a subjective scale. Strong diffuse staining for IMP3 was observed in 31% (24 of 77) of tumors and associated with a shorter progression-free survival (hazard ratio, 2.63; p = 0.008). This cohort confirmed previously identified prognostic factors, including extent of resection, age, and tumor location. Currently, only clinical factors are weighed to stratify risk for patients and to identify those who should receive further therapy. Multivariate analyses identified IMP3 expression as an independent prognostic factor when combined with high-/low-risk stratification (hazard ratio, 2.45; p = 0.016). High IMP3, as assessed by immunohistochemistry, has potential use as an additional predictor of poor prognosis in pediatric PA/PMAs and warrants evaluation in larger cohorts.
Modern chemoimmunotherapies have produced higher response rates and improved survival in mantle cell lymphoma (MCL); however, disease relapse remains a challenge. The availability of various post-remission maintenance or consolidation strategies, have led some to question the role of upfront autologous hematopoietic cell transplantation (auto-HCT) consolidation for MCL, in the chemoimmunotherapy-era. A one size fits all approach is no longer appropriate for MCL in first remission, and the choice of preferred post-remission (observation, maintenance or consolidation) strategy is increasingly becoming a factor of patient age, comorbidities and disease risk stratification. In select low-risk patients (based on Mantle cell lymphoma International Prognostic Index (MIPI)), observation following rituximab plus Hyper-CVAD-like inductions seems appropriate. Rituximab maintenance after anthracycline-based chemoimmunotherapies in elderly transplant ineligible patients has shown survival benefit and should be considered a valid option. Limited studies suggest feasibility of radioimmunotherapy consolidation in first remission; however, in the absence of randomized data, this modality remains investigational. In younger, transplant-eligible patients receiving cytarabine-containing inductions, upfront consolidation with auto-HCT has shown survival benefit, and remains a standard-of-care option in the modern-era. Hyper-CVAD associated stem cell mobilization failure is an increasingly recognized problem, underscoring the need for alternative inductions, or consideration for early stem cell collection, when this induction regimen is used. Outcomes of high-risk MIPI patients remain suboptimal with currently available induction and post-remission strategies and represents an area where adoptive immunotherapy in the form of allogeneic-HCT warrants investigation. Incorporation of novel MoAbs and targeted agents (PI3K inhibitors, mTOR inhibitors, BTK inhibitors and so on.) in maintenance and consolidation strategies will build on the significant therapeutic gains of last decade, in coming years.Bone Marrow Transplantation advance online publication, 15 April 2013; doi:10.1038/bmt.2013.56.
[Bleeding origin, patient-related risk factors, and prognostic indicators in patients with acute gastrointestinal hemorrhages requiring intensive care treatment : A retrospective analysis from 1999 to 2010.]
- Medizinische Klinik, Intensivmedizin und Notfallmedizin
- Published about 7 years ago
BACKGROUND: Gastrointestinal bleeding (GIB) is a common problem in elderly patients involving severe comorbidities and concomitant antiplatelet or anticoagulatory therapy. The risk factors and prognostic indicators of patients with severe GIB requiring intensive care medical treatment have not been well evaluated. METHODS: A retrospective analysis of 7,376 patients from the medical intensive care unit (ICU) at the University Hospital Aachen was carried out between 1999 and 2010. RESULTS: Of 614 patients admitted to the ICU because of acute GIB, 463 (75%) presented with upper GIB (UGIB) and 151 (25%) with lower GIB (LGIB). Despite early endoscopic intervention and ICU treatment, UGIB had a mortality rate of 16%, whereas LGIB showed a significantly better prognosis (mortality <5%) in the ICU setting. Risk factors for OGIB-related mortality were hemodynamic instability, organ failure, comorbidities (especially liver cirrhosis), and rebleeding. In total, 218 patients (36%) were treated with antiplatelet or anticoagulatory drugs, which were associated with a favorable prognosis in the UGIB group. Elevated serum lactate levels upon admission were superior in predicting mortality than established indicators of prognosis such as the Rockall or the Glasgow-Blatchford score. CONCLUSIONS: Despite successful endoscopic intervention, severe acute UGIB is associated with a significant mortality rate of 16% in the ICU setting, determined by hemodynamic failure, organ dysfunction, and comorbidities. The serum lactate levels of patients with GIB on the day of admission to the ICU are prognostic.
In order to determine the relationship between expression of cyclic nucleotide phosphodiesterase isoform 7B (PDE7B) and mantle cell lymphoma (MCL) progression, PDE7B mRNA expression was measured by qRT-PCR in 21 untreated MCL patients with bone marrow involvement and 20 healthy donors. The expression level of PDE7B was markedly higher in MCL patients compared with normal controls (P=0.001), and the higher level of PDE7B expression was associated with unfavorable cytogenetic characteristics in MCL. It was showed that higher expression of PDE7B might be a novel unfavorable prognostic indicator in MCL, which possess important clinical significance.
BACKGROUND: Nontraumatic impaired consciousness is a common issue in emergency departments with a serious but widely variable prognosis. STUDY OBJECTIVES: The aim of this prospective study was to evaluate the ability of systematic combined noncontrast computed tomography (NCCT)/computed tomography angiography (CTA) imaging, firstly to provide a neurologic prognosis and secondly to ensure early detection of basilar artery occlusion (BAO), in unexplained nontraumatic impaired consciousness management. METHODS: Combined NCCT/CTA imaging was performed on 65 patients with impaired consciousness and no history of trauma prospectively over 14 months in a single center. Images were assessed based on visual and quantitative criteria. Clinical outcome was assessed using the modified Rankin Scale at 3 months. Statistical analysis aimed to identify the prognostic value of combined NCCT/CTA imaging and its ability for early BAO detection. RESULTS: This study shows that combined NCCT/CTA imaging was a significant predictor of poor neurological outcome, with a positive predictive value of 94.6%. The combination was also crucial for early detection of BAO, given that 42.8% of cases were misdiagnosed with NCCT alone. Basilar artery occlusion represented 10.8% of all unexplained nontraumatic impaired consciousness. CONCLUSIONS: Systematic combined NCCT/CTA imaging is an efficient tool for predicting poor neurologic prognosis in cases of unexplained nontraumatic impaired consciousness and is also essential for detecting BAO.