Noncoding RNome as Enabling Biomarkers for Precision Health.

Noncoding RNAs (ncRNAs), in the form of structural, catalytic or regulatory RNAs, have emerged to be critical effectors of many biological processes. With the advent of new technologies, we have begun to appreciate how intracellular and circulatory ncRNAs elegantly choreograph the regulation of gene expression and protein function(s) in the cell. Armed with this knowledge, the clinical utility of ncRNAs as biomarkers has been recently tested in a wide range of human diseases.

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics.

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests.

Development and validation of a circulating microRNA panel for the early detection of breast cancer.

Background: Mammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening.

Methods: This study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379).

Advances in quantifying circulatory microRNA for early disease detection.

Precision preventive healthcare aims to improve patient health by integrating preventive measures with early disease detection for timely intervention with precision medicine. Key to the delivery of preventive healthcare is the clinical adoption of novel assays that enable early disease detection. Such assays, typically based on biomarkers such as microRNAs (miRNAs) from liquid biopsy or excreta, are entering clinical practice after years of clinical development and validation.

Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer.

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively.

Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population.

Objective: An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population.

Design: We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea.

Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

Background: Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers.

Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library.

Background: While there is strong evidence for phosphatidylinositol 3-kinase (PI3K) involvement in cancer development, there is limited information about the role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K regulatory subunit p55γ, is over-expressed in glioblastoma and ovarian cancers, but its expression in gastric cancer (GC) is not known. We thus used genetic and bioinformatic approaches to examine PIK3R3 expression and function in GC, the second leading cause of cancer mortality world-wide and highly prevalent among Asians.

DNA-directed assembly of protein microarrays.

Microarray technology has made it possible to simultaneously study the abundance, interactions, and functions of potentially tens of thousands of biological molecules. From its earliest use in DNA microarrays, where only nucleic acids were captured and detected on the arrays, applications of microarrays now extend to those involving biomolecules such as antibodies, proteins, peptides, and carbohydrates. In contrast to the relative robustness of DNA microarrays, the use of such chemically diverse biomolecules on microarray formats presents many challenges in their fabrication as well as application.

Spatially addressable protein array: ssDNA-directed assembly for antibody microarray.

Protein microarray offers a means for high-throughput profiling of cellular proteins to provide insights into the mechanisms of biological processes. This study describes the design and fabrication of a robust platform, spatially addressable protein array (SAPA), by exploring the specificity of ssDNA hybridization for self-assembly of semi-synthetic ssDNA-antibody conjugates which capture antigens from complex biological samples. This approach does not involve the direct immobilization of antibodies nor antigen, but instead captures the target antigens in the solution phase followed by self-directed assembly of the complex onto the surface.

Carboxyl-terminated dendrimer-coated bioactive interface for protein microarray: high-sensitivity detection of antigen in complex biological samples.

Protein microarrays are promising tools that can potentially enable high throughput proteomic screening in areas such as disease diagnosis and drug discovery. A critical aspect in the development of protein microarrays is the optimization of the array's surface chemistry to achieve the high sensitivity required for detection of proteins in cell lysate and other complex biological mixtures. In the present study, a high-density antibody array with minimal nonspecific cellular protein adsorption was prepared using a glass surface coated with a poly(propyleneimine) dendrimer terminated with carboxyl group (PAMAM-COOH).