Cancer Transcriptome Profiling at the Juncture of Clinical Translation !

Next-Generation Sequencing

Methodological breakthroughs over the past four decades have repeatedly revolutionized transcriptome profiling. Using RNA sequencing (RNA-seq), it has now become possible to sequence and quantify the transcriptional outputs of individual cells or thousands of samples. These transcriptomes provide a link between cellular phenotypes and their molecular underpinnings, such as mutations. In the context of cancer, this link represents an opportunity to dissect the complexity and heterogeneity of tumours and to discover new biomarkers or therapeutic strategies. Here, we review the rationale, methodology and translational impact of transcriptome profiling in cancer.

Transcriptomics is the large-scale study of RNA molecules by use of high-throughput techniques. It examines the abundance and makeup of a cell's transcriptome. In contrast to DNA, which is largely identical across all cells of an organism, the actively transcribed RNA is highly dynamic, reflecting the diversity of cell types, cellular states and regulatory mechanisms. Because a transcriptome profile can be regarded as a signature or snapshot of the underlying cell state, the experimental profiling of samples and specimens can provide insights into their unique biology.

Depending on the specific approach, transcriptomics can not only reveal the architecture of gene expression but also provide details on the structure, modification and variation of individual transcripts. Advances in transcriptome profiling, specifically the development of genome-wide methodologies targeting diverse RNA species, have enabled us to discover the seemingly endless complexity of RNA biology and to comprehensively annotate the human genome and other eukaryotic genomes. Arguably, transcriptomics is currently the most well-established modality and foundation of functional genomics, a field of study for which the goal is to synthesize large-scale data to understand the mechanisms that govern cellular and organismal phenotypes.

• RNA sequencing (RNA-seq) has the potential to bridge tumour genotypes (for example, mutations) and their phenotypic consequences (for example, cancer molecular subtypes).
• The field of transcriptomics has matured thanks to lockstep developments in experimental protocols, algorithms and databases.
• Methodological and algorithmic advances continue to enable clinical applications of transcriptome profiling.
• Detection of gene fusions is the most immediate application of RNA-seq.
• Gene expression signatures have demonstrated prognostic and predictive value.
• Transcriptome profiling will be essential for immuno-oncology.

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MicroRNA: A Tiny Molecule Yields Big Insights Into Disease States

Regular readers of this column will know that there are two main categories of nucleic acids—DNA and RNA. They’ll also know that while for living organisms DNA acts as the genetic data repository, RNA has a messenger role (mRNAs, transcribed from DNA to direct protein synthesis). Most will also recall that there are other classes of RNA molecules, particularly tRNAs (used to tag and identify amino acids for protein synthesis) and rRNAs (structural components of the ribosome, the cellular “machinery” for protein synthesis). In addition to these, there’s increasing interest in the molecular diagnostics community in a less widely known but no less common RNA form, the microRNA or miRNA.

Read more: MicroRNA: A Tiny Molecule Yields Big Insights Into Disease States

Source: MedicalLaboratoryObserver

Electrical Immunosensor Detects Acute Myocardial Infarction

Heart disease and especially acute myocardial infarction (AMI) are the leading causes of death for both men and women and therefore, a fast and reliable diagnosis of heart attack or cardiac episode are urgently needed.

The most commonly used biomarkers are creatine kinase-MB, myoglobin, cardiac troponin T, and cardiac troponin I (cTnI), which is a subunit of the troponin complex found in cardiac muscle and is a highly specific and sensitive biomarker for the clinical diagnosis of AMI.

Read more: Electrical Immunosensor Detects Acute Myocardial Infarction

The core material used for the new immunosensor that detects proteins in the blood stream following

a heart attack, providing results in just one minute (Photo courtesy of Ulsan National Institute of

Science and Technology).

Source: labmedica

Current Approaches for the Detection of Acute Kidney Injury

Acute kidney injury (AKI) is a recognized complication in hospitalized patients. A report in 2009 from National Confidential Enquiry into Patient Outcome and Death (NCEPOD) suggested that AKI was frequently undetected in hospital patients thus contributing to patient morbidity and mortality. Clinical guidelines for recognition and treatment for acute kidney injury were published by NICE (the National Institute for Health and Care Excellence) in 2013 and reported an associated mortality with AKI of more than 25–30%. This guideline also recognized the prevalence of AKI in the primary care population in patients with or without acute illness. NICE also recognized the impact of AKI on healthcare resources, with costs (excluding those in the community) of £434–620 million per year, more than that associated with breast, lung and skin cancer combined

AKI is characterized by an acute loss of the kidney’s excretory capacity leading to accumulation of waste products such as urea and creatinine, and decreased urine output. It is associated with rapid decline in glomerular filtration rate and increases in potassium, phosphate and hydrogen ions. It has varied causes and may be secondary to a non-renal event, thus may be common in hospitalized patients and critically ill patients. It may go undetected in primary care as it can occur without any symptoms. There are associations between co-morbidities, current medications, acute illness and AKI resulting in the high morbidity associated with the condition and the impact on healthcare resources.

Read more: Current Approaches for the Detection of Acute Kidney Injury

Source: cli-online

Plasma Levels Investigated as Alzheimer's Disease Biomarkers

The relationship between plasma levels of two amyloid beta peptides (Aβ1-40 and Aβ1-42), brain volumetrics and cognitive performance has been investigated.

Since amyloid beta (Aβ) peptides are the main component of the amyloid plaques found in Alzheimer patients' brains, changes in levels of Aβ in blood plasma may provide a biomarker for detecting increased risk or early diagnosis of disease.

Scientists at the University of New South Wales (Sydney, Australia) examined 126 age-matched cognitively normal controls, 89 individuals with amnestic mild cognitive impairment (aMCI,) from the Center for Healthy Brain Aging (CHeBA) Sydney Memory & Aging Study (Sydney MAS), as well as 39 individuals with Alzheimer's disease (AD) recruited from a specialty clinic.

Read more: Plasma Levels Investigated as Alzheimer's Disease Biomarkers

A diagram of the formation of amyloid plaques in the brain of an Alzheimer brain compared
with a normal brain

Source: Junji Takano

Standardizing Immunoassays: The Benefits of Conformity

Interpreting results of immunoassay-based methods frequently presents a challenge for physicians, especially when caring for patients at multiple institutions that use different assay platforms. For many analytes including tumor markers, endocrine hormones, and cardiac biomarkers, results generated on different platforms are not directly comparable. This is due to the absence of a universally accepted reference material, which manufacturers need to calibrate their assays to a common standard.

Instead, test results must be interpreted using assay-specific reference intervals—a concept that comes naturally to clinical laboratorians but often is foreign to many physicians and patients. This lack of uniform results causes confusion that can adversely affect patient care, particularly when patients are diagnosed at one hospital but pursue follow-up care elsewhere. For example, does an increased CA-125 value at follow-up at a different institution reflect disease progression or simply differences in assay calibration? A lack of standardization also makes it impossible to transfer diagnostic cutoffs from one institution to another unless the assay platforms are identical.

Given the confusion associated with non-standardized assays, why haven’t all immunoassays already been standardized?

Read more: Standardizing Immunoassays: The Benefits of Conformity

Source: alfa