Quantitative Integrative Survival Prediction in Multiple Myeloma Patients Treated With Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation.

Purpose: Given the high heterogeneity in survival for patients with multiple myeloma, it would be clinically useful to quantitatively predict the individual survival instead of attributing patients to two to four risk groups as in current models, for example, revised International Staging System (R-ISS), R2-ISS, or Mayo-2022-score.

Patients And Methods: Our aim was to develop a quantitative prediction tool for individual patient's 3-/5-year overall survival (OS) probability. We integrated established clinical and molecular risk factors into a comprehensive prognostic model and evaluated and validated its risk discrimination capabilities versus R-ISS, R2-ISS, and Mayo-2022-score.

Molecular Long-Term Analysis of the GMMG-HD4 Trial in Multiple Myeloma-Patterns of Association of Chromosomal Aberrations with Response and Proliferation Determining Survival in Selecting Treatments in View of Limited Resources in Low- and Middle-Income Countries.

Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g.

Prevalence of the GFI1-36N SNP in Multiple Myeloma Patients and Its Impact on the Prognosis.

Transcription factor Growth Factor Independence 1 (GFI1) regulates the expression of genes important for survival, proliferation and differentiation of hematopoietic cells. A single nucleotide polymorphism (SNP) variant of GFI1 (GFI1-36N: serine replaced by asparagine at position 36), has a prevalence of 5-7% among healthy Caucasians and 10-15% in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) predisposing GFI-36N carriers to these diseases. Since GFI1 is implicated in B cell maturation and plasma cell (PC) development, we examined its prevalence in patients with multiple myeloma (MM), a haematological malignancy characterized by expansion of clonal PCs.

CXCL9 Predicts Severity at the Onset of Chronic Graft-versus-host Disease.

Background: Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality.

EASIX for prediction of survival in lower-risk myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) are at risk of early death from cardiovascular complications due to the link between clonal hematopoiesis and endothelial dysfunction. EASIX (Endothelial Activation and Stress Index) has been established to predict endothelial complications after allogeneic transplantation. We investigated the impact of EASIX measured at first diagnosis on survival of patients with lower- and higher-risk MDS (no allogeneic transplantation) in two independent institutions: n = 192 (training cohort) and n = 333 (validation cohort).

Marginal variable screening for survival endpoints.

When performing survival analysis in very high dimensions, it is often required to reduce the number of covariates using preliminary screening. During the last years, a large number of variable screening methods for the survival context have been developed. However, guidance is missing for choosing an appropriate method in practice.

No Evidence for Effect of Exercise on Transcriptome of NK Cells in Breast Cancer Patients Undergoing Adjuvant Therapy: Results From a Pilot Study.

Background: Mobilization and activation of natural killer cells (NK cells) have been hypothesized to contribute to observed protective effects of exercise on cancer development and progression. Some evidence exists for acute effects of aerobic exercise on NK cell mobilization and function, i.e.

Association of resilience with health-related quality of life and depression in multiple myeloma and its precursors: results of a German cross-sectional study.

Objectives: To investigate the relation between resilience, health-related quality of life (HRQOL) and depression in multiple myeloma (MM) and its premalignant stages. MM is one of the most frequent haematological disorders. It is regularly preceded by asymptomatic stages of the disease namely monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM).

Multiple-rater kappas for binary data: Models and interpretation.

Interrater agreement on binary measurements with more than two raters is often assessed using Fleiss' κ, which is known to be difficult to interpret. In situations where the same raters rate all items, however, the far less known κ suggested by Conger, Hubert, and Schouten is more appropriate. We try to support the interpretation of these characteristics by investigating various models or scenarios of rating.

Clustering of samples and variables with mixed-type data.

Analysis of data measured on different scales is a relevant challenge. Biomedical studies often focus on high-throughput datasets of, e.g.

miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer.

Lung cancer is one of the most aggressive tumours with very low life expectancy. Altered microRNA expression is found in human tumours because it is involved in tumour growth, progression and metastasis. In this study, we analysed microRNA expression in 47 lung cancer biopsies.

Gene expression changes in blood RNA after swimming in a chlorinated pool.

Exposure to disinfection by-products (DBP) such as trihalomethanes (THM) in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40min in an indoor chlorinated pool.

Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.

Background: cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown.

Results: Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways.

Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets.

With the number of prognostic and predictive genetic markers in neuro-oncology steadily growing, the need for comprehensive molecular analysis of neuropathology samples has vastly increased. We therefore developed a customized enrichment/hybrid-capture-based next-generation sequencing (NGS) gene panel comprising the entire coding and selected intronic and promoter regions of 130 genes recurrently altered in brain tumors, allowing for the detection of single nucleotide variations, fusions, and copy number aberrations. Optimization of probe design, library generation and sequencing conditions on 150 samples resulted in a 5-workday routine workflow from the formalin-fixed paraffin-embedded sample to neuropathological report.

Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor.

Background: Epidermal Growth Factor (EGF) plays an important function in the regulation of cell growth, proliferation, and differentiation by binding to its receptor (EGFR) and providing cancer cells with increased survival responsiveness. Signal transduction carried out by EGF has been extensively studied at both transcriptional and post-transcriptional levels. Little is known about the involvement of microRNAs (miRNAs) in the EGF signaling pathway.

Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis.

Background: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer.

Results: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment.

Molecular profiles and clinical outcome of stage UICC II colon cancer patients.

Purpose: Published multigene classifiers suggesting outcome prediction for patients with stage UICC II colon cancer have not been translated into a clinical application so far. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable their reconstruction in routine diagnostic specimens.

Methods: Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of previously published prognostic classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A).

TEQC: an R package for quality control in target capture experiments.

Unlabelled: TEQC is an R/Bioconductor package for quality assessment of target enrichment experiments. Quality measures comprise specificity and sensitivity of the capture, enrichment, per-target read coverage and its relation to hybridization probe characteristics, coverage uniformity and reproducibility, and read duplicate analysis. Several diagnostic plots allow visual inspection of the data quality.

Tumor infiltrated hilar and mediastinal lymph nodes are an independent prognostic factor for decreased survival after pulmonary metastasectomy in patients with renal cell carcinoma.

Purpose: Surgical resection remains the most effective treatment in patients with pulmonary metastasis of renal cell carcinoma. To our knowledge the prognostic significance of mediastinal and hilar lymph node metastasis during pulmonary metastasectomy in patients with renal cell carcinoma is unknown. We analyzed the value of computerized tomography to predict mediastinal/hilar lymph node involvement as well as the impact of systematic lymphadenectomy on survival in patients with pulmonary renal cell carcinoma metastasis.

MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation.

Background: Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis.

ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays.

Purpose: Recently, several novel molecular prognostic markers were identified in cytogenetically normal acute myeloid leukemia (CN-AML). In addition to the well-known influence of FLT3, NPM1, and CEBPA mutations, high transcript levels of the ERG, BAALC, and MN1 genes have been associated with inferior outcomes, but the relative importance of these risk markers remains to be defined.

Patients And Methods: We analyzed ERG, BAALC, and MN1 expression levels in a cohort of 210 patients with CN-AML who received intensive chemotherapy.

Increased expression of cell-cell signaling genes by stimulated mononuclear leukocytes in patients with previous atherothrombotic stroke. A whole genome expression profile study.

Background/aims: Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke.

Methods: In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes.

Strategies for a reliable biostatistical analysis of differentially expressed spots from two-dimensional electrophoresis gels.

We performed quantitative comparisons with the two-dimensional gel electrophoresis technique and evaluated the reliability of biostatistical tests for the correction of "false significant" results (alpha-error) by performing repeated runs of an experiment. Results based on uncorrected p-values yielded numerous significant differences in spot intensity which could not be replicated in two additional runs. The best strategy for avoiding these "false-positive" results was strongly dependent on the type of result.

An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature.