RNA-seq validation of microRNA expression signatures for precision melanoma diagnosis and prognostic stratification.

Background: New diagnostic tools are needed to improve the diagnosis and risk stratification of cutaneous melanoma. Disease-specific microRNA signatures have been previously described via NanoString profiling of solid biopsy tissue and plasma. This study validated these signatures via next-generation sequencing technology and compared their performance against clinical metrics and other published melanoma signatures.

Validation of a microRNA liquid biopsy assay for diagnosis and risk stratification of invasive cutaneous melanoma.

Background: Noninvasive molecular biomarkers are needed to improve the early, accurate and precise diagnosis of invasive cutaneous melanoma.

Objectives: To independently validate a previously identified circulating microRNA signature of melanoma (MEL38), and, secondly, to develop a complementary microRNA signature, optimized for prognostication.

Patients And Methods: MicroRNA expression profiling was performed on plasma samples from a multicentre observational case-control study, involving patients with primary or metastatic melanoma, melanoma in situ, nonmelanoma skin cancer, or benign naevi.

Translation of a circulating miRNA signature of melanoma into a solid tissue assay to improve diagnostic accuracy and precision.

Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-miRNA signature (MEL38) was identified in melanoma patient plasma and validated as a novel biomarker.

Characterisation and validation of Mel38; A multi-tissue microRNA signature of cutaneous melanoma.

Background: Histopathologic examination of melanocytic neoplasms can be challenging and subjective, with no specific circulating or tissue-based biomarkers currently available. Recently, a circulating 38-microRNA profile of melanoma (Mel38) was described. In this study, Mel38 expression and its impact on downstream mRNA regulation in solid tissue is examined.

A plasma microRNA biomarker of melanoma as a personalised assessment of treatment response.

New tools for monitoring response to primary melanoma treatment are needed to reduce recurrence rates and patient anxiety. A previously developed plasma-based microRNA signature (MEL38) was measured in four melanoma patient samples obtained before and 12-14 days after treatment (i.e.

Development and validation of a plasma-based melanoma biomarker suitable for clinical use.

This corrects the article DOI: 10.1038/bjc.2017.

Gene expression profiling during intensive cardiovascular lifestyle modification: Relationships with vascular function and weight loss.

Heart disease and related sequelae are a leading cause of death and healthcare expenditure throughout the world. Although many patients opt for surgical interventions, lifestyle modification programs focusing on nutrition and exercise have shown substantial health benefits and are becoming increasing popular. We conducted a year-long lifestyle modification program to mediate cardiovascular risk through traditional risk factors and to investigate how molecular changes, if present, may contribute to long-term risk reduction.

Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification.

Objective: To examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles.

Methods: A prospective nonrandomized trial was conducted over 1 year in participants undergoing intensive lifestyle modification to reverse or stabilize progression of coronary artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene expression as a function of weight loss were assessed in 89 lifestyle participants and 71 retrospectively matched controls undergoing usual care.

Translating a gene expression signature for multiple myeloma prognosis into a robust high-throughput assay for clinical use.

Background: Widespread adoption of genomic technologies in the management of heterogeneous indications, including Multiple Myeloma, has been hindered by concern over variation between published gene expression signatures, difficulty in physician interpretation and the challenge of obtaining sufficient genetic material from limited patient specimens.

Methods: Since 2006, the 70-gene prognostic signature, developed by the University of Arkansas for Medical Sciences (UAMS) has been applied to over 4,700 patients in studies performed in 4 countries and described in 17 peer-reviewed publications. Analysis of control sample and quality control data compiled over a 12-month period was performed.

Gene expression differences in adipose tissue associated with breast tumorigenesis.

Long thought to function only as an inert energy storage depot, the role of adipose tissue in breast tumorigenesis has been largely ignored. In light of increasing rates of obesity and use of breast conserving therapy and autologous fat grafting, improved understanding of the role of adipose tissue in tumor etiology is crucial. Thus, adipose tissue adjacent to and distant from invasive breast tumors (n = 20), or adjacent to non-malignant diagnoses (n = 20) was laser microdissected from post-menopausal women.

Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function.

Background: Healthy lifestyle changes are thought to mediate cardiovascular disease risk through pathways affecting endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. We examined the effect of a rigorous cardiovascular disease risk reduction program on peripheral blood gene expression profiles in 63 participants and 63 matched controls to characterize molecular responses and identify regulatory pathways important to cardiovascular health.

Methods And Results: Dramatic changes in dietary fat intake (-61%; P<0.

BreastPRS is a gene expression assay that stratifies intermediate-risk Oncotype DX patients into high- or low-risk for disease recurrence.

Molecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tumor samples to translate the assay to FFPE.

Recreational Music-Making alters gene expression pathways in patients with coronary heart disease.

Background: Psychosocial stress profoundly impacts long-term cardiovascular health through adverse effects on sympathetic nervous system activity, endothelial dysfunction, and atherosclerotic development. Recreational Music Making (RMM) is a unique stress amelioration strategy encompassing group music-based activities that has great therapeutic potential for treating patients with stress-related cardiovascular disease.

Material/methods: Participants (n=34) with a history of ischemic heart disease were subjected to an acute time-limited stressor, then randomized to RMM or quiet reading for one hour.

Effect of ASCO/CAP guidelines for determining ER status on molecular subtype.

Background: Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1% positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype.

Genomic signatures for predicting survival and adjuvant chemotherapy benefit in patients with non-small-cell lung cancer.

Background: Improved methods are needed for predicting prognosis and the benefit of delivering adjuvant chemotherapy (ACT) in patients with non-small-cell lung cancer (NSCLC).

Methods: A novel prognostic algorithm was identified using genomic profiles from 332 stage I-III adenocarcinomas and independently validated on a separate series of 264 patients with stage I-II tumors, compiled from five previous studies. The prognostic algorithm was used to interrogate genomic data from a series of patients treated with adjuvant chemotherapy.

Design and multiseries validation of a web-based gene expression assay for predicting breast cancer recurrence and patient survival.

Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors.

Implementation of a novel microarray-based diagnostic test for cancer of unknown primary.

Patients with carcinoma of unknown primary (CUP) present with metastatic disease for which the primary site cannot be found, despite extensive standard investigation. Here, we describe the development and implementation of the first clinically available microarray-based test for this cancer type (CUPPrint), based on 633 individual tumors representing 30 carcinoma and 17 noncarcinoma classes. Tissue of origin prediction for either fresh frozen or paraffin-embedded tumor samples is achieved with the use of a custom 8-pack 1.

Gene expression profiling to identify the histogenetic origin of metastatic adenocarcinomas of unknown primary.

Purpose: Patients with adenocarcinoma of unknown primary origin (ACUP) constitute approximately 4% of all malignancies. For effective treatment of these patients, it is considered optimal to identify the primary tumor origins. Currently, the success rate of the diagnostic work-up is only 20% to 30%.

Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen.

Background: Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancer patients treated with first-line tamoxifen for metastatic disease.

Methods: From a consecutive series of 246 estrogen receptor (ER) positive primary tumors, gene expression profiling was performed on available frozen tumors using 44K oligoarrays (n = 69).

Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma.

Purpose: Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis-with death within 3 years of diagnosis-most often due to transformation to aggressive disease.

Patients And Methods: In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.

Results: At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting.

Empirical array quality weights in the analysis of microarray data.

Background: Assessment of array quality is an essential step in the analysis of data from microarray experiments. Once detected, less reliable arrays are typically excluded or "filtered" from further analysis to avoid misleading results.

Results: In this article, a graduated approach to array quality is considered based on empirical reproducibility of the gene expression measures from replicate arrays.

Location of, immunogenicity of and relationships between neutralization epitopes on the attachment protein (G) of Hendra virus.

Epitopes involved in a protective immune response to Hendra virus (HeV) (Henipavirus, Paramxyoviridae) were investigated by generating five neutralizing monoclonal antibodies (mAbs) to the virus attachment protein (G) of HeV (HeV G) and sequencing of the G gene of groups of neutralization-escape variants selected with each mAb. Amino acid substitutions occurred at eight distinct sites on HeV G. Relationships between these sites were investigated in binding and neutralization assays using heterologous combinations of variants and mAbs.

An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin.

Gene expression profiling offers a promising new technique for the diagnosis and prognosis of cancer. We have applied this technology to build a clinically robust site of origin classifier with the ultimate aim of applying it to determine the origin of cancer of unknown primary (CUP). A single cDNA microarray platform was used to profile 229 primary and metastatic tumors representing 14 tumor types and multiple histologic subtypes.

Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors.

Histone deacetylase inhibitors (HDACis) inhibit tumor cell growth and survival, possibly through their ability to regulate the expression of specific proliferative and/or apoptotic genes. However, the HDACi-regulated genes necessary and/or sufficient for their biological effects remain undefined. We demonstrate that the HDACis suberoylanilide hydroxamic acid (SAHA) and depsipeptide regulate a highly overlapping gene set with at least 22% of genes showing altered expression over a 16-h culture period.

Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix.

A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.