Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma.

Background: In melanoma, there is no companion diagnostic test to predict response to programmed cell death 1 (PD-1) axis immune checkpoint inhibitor (ICI) therapy. In the adjuvant setting, only one in five patients may benefit from ICI, so a biomarker is needed to select those that may or may not benefit. Here, we test a new 4-gene multiplex immunotherapy panel with research use only (RUO) prototype mRNA expression profile on the GeneXpert closed system using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) for association with clinical benefit after treatment with ICI therapy in metastatic melanoma patients.

Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer.

We quantified human epidermal growth factor receptor 2 (HER2) RNA and protein expression in 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in situ hybridization (ISH) group 4 ( () ratio <2.0, average copy number ≥4.0 and <6.

DNA Methylation Markers for Breast Cancer Detection in the Developing World.

Purpose: An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA). Two case-control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection/training ( = 226) and testing ( = 246).

Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer.

Background: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.

Objective: To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC.

Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer.

An on-demand, closed RT-qPCR, the GeneXpert (GX) system, has the potential to provide biomarker information in low-resourced settings and elsewhere. We used this system with a research use only version of the Breast Cancer STRAT4 cartridge that measures the mRNA expression levels of ERBB2, ESR1, PGR, and MKi67. Here we evaluated the impact of non-macrodissected (non m-d) versus macrodissected (m-d) samples using STRAT4 on formalin-fixed, paraffin-embedded (FFPE) core needle biopsies.

Peripheral blood gene expression signatures which reflect smoking and aspirin exposure are associated with cardiovascular events.

Background: Cardiovascular disease and its sequelae are major causes of global mortality, and better methods are needed to identify patients at risk for future cardiovascular events. Gene expression analysis can inform on the molecular underpinnings of risk factors for cardiovascular events. Smoking and aspirin have known opposing effects on platelet reactivity and MACE, however their effects on each other and on MACE are not well described.

An age- and sex-specific gene expression score is associated with revascularization and coronary artery disease: Insights from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial.

Background: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority.

Methods: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in symptomatic nondiabetic patients in the PROMISE trial. The outcomes were oCAD (≥70% stenosis in ≥1 vessel or ≥50% left main stenosis on CT angiography [CTA]) and a composite endpoint of death, myocardial infarction, revascularization, or unstable angina.

Developing Peripheral Blood Gene Expression-Based Diagnostic Tests for Coronary Artery Disease: a Review.

The past 20 years has witnessed the development of technologies designed to measure changes in the expressed human genome, including the levels of RNA transcripts, proteins, and metabolites. Gene expression profiling, or the measurement of RNA transcripts, allows investigators to obtain a snapshot of a subject's current physiological state and may be used to assess disease likelihood. In this review, we provide an overview of recent work using peripheral blood gene expression to assess coronary artery disease (CAD) and discuss the best approaches for developing and validating tests utilizing such gene expression signatures.

Use of a blood test incorporating age, sex, and gene expression influences medical decision-making in the evaluation of women presenting with symptoms suggestive of obstructive coronary artery disease: summary results from two ambulatory care studies in primary care.

Objective: Clinicians need better approaches to evaluating women at midlife and beyond who present to primary care with chest pain and related symptoms. A previously validated blood-based test, which includes age, sex, and gene expression levels, showed a 96% negative predictive value for determining an individual's current likelihood of having obstructive coronary artery disease (CAD) in a combined population of men and women. We hypothesized that age/sex/gene expression score (ASGES) would be incorporated into medical decision-making and would influence the rate of further cardiac evaluation.

Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies.

A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC)=0.

Utility of a genomic-based, personalized medicine test in patients presenting with symptoms suggesting coronary artery disease.

Purpose: Better methods are needed to assess patients presenting with symptoms suggestive of obstructive coronary artery disease (CAD). We hypothesized that the use of a gene expression score (GES) would lead to a change in the diagnostic evaluation.

Methods: The Primary Care Providers Use of a Gene Expression Test in Coronary Artery Disease Diagnosis (IMPACT-PCP) trial (clinical trial identifier NCT01594411, clinicaltrials.

Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood.

Background: Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18).

Methods: Blood samples were collected from 1014 patients at 13 US clinic locations before they underwent an invasive prenatal procedure.

Assessment of clinical validity of a breast cancer risk model combining genetic and clinical information.

Background: The Gail model is widely used for the assessment of risk of invasive breast cancer based on recognized clinical risk factors. In recent years, a substantial number of single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified. However, it remains unclear how to effectively integrate clinical and genetic risk factors for risk assessment.

Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures.

Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9,704 white women were recruited at four U.S.

C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study.

Objective: C-reactive protein (CRP) gene variation, in particular an rs2794521 variant was recently associated with type 2 diabetes mellitus (T2DM) in Pima Indians.

Research Design And Methods: The present investigation was conducted to replicate this previous association, and to further examine the potential association of a set of common CRP gene variants with the prevalence of T2DM in a case-control investigation. A total of 629 T2DM cases (476 Whites, and 153 Blacks), and 579 controls (481 Whites, and 98 Blacks) were examined.

The effect of insulin on expression of genes and biochemical pathways in human skeletal muscle.

To study the insulin effects on gene expression in skeletal muscle, muscle biopsies were obtained from 20 insulin sensitive individuals before and after euglycemic hyperinsulinemic clamps. Using microarray analysis, we identified 779 insulin-responsive genes. Particularly noteworthy were effects on 70 transcription factors, and an extensive influence on genes involved in both protein synthesis and degradation.

Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women.

Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent.

Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status.

Background And Purpose: Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States.

Methods: The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.

Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2.

We report a genomewide linkage study of type 2 diabetes (T2D [MIM 125853]) in the Icelandic population. A list of type 2 diabetics was cross-matched with a computerized genealogical database clustering 763 type 2 diabetics into 227 families. The diabetic patients and their relatives were genotyped with 906 microsatellite markers.