Spatial domain analysis predicts risk of colorectal cancer recurrence and infers associated tumor microenvironment networks.

An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. Here, we develop a transformational spatial analytics computational and systems biology platform (SpAn) that predicts clinical outcomes and captures emergent spatial biology that can potentially inform therapeutic strategies. We apply SpAn to primary tumor tissue samples from a cohort of 432 chemo-naïve colorectal cancer (CRC) patients iteratively labeled with a highly multiplexed (hyperplexed) panel of 55 fluorescently tagged antibodies.

NDRG1 regulates neutral lipid metabolism in breast cancer cells.

Background: Altered lipid metabolism is an emerging hallmark of aggressive breast cancers. The N-myc downstream regulated gene (NDRG1) gene plays a critical role in peripheral nervous system myelination, as inactivating mutations cause severe demyelinating neuropathy. In breast cancer, elevated NDRG1 expression has been linked to clinical outcomes, but its functional role in breast cancer physiology has remained unclear.

Single-Cell Mass Spectrometry of Subpopulations Selected by Fluorescence Microscopy.

Specific subpopulations in a heterogeneous collection of cells, for example, cancer stem cells in a tumor, are often associated with biological or medical conditions. Fluorescence microscopy, based on biomarkers labeled with fluorescent probes, is a widely used technique for the visualization and selection of such cells. Phenotypic differences for these subpopulations at the molecular level can be identified by their untargeted analysis by single-cell mass spectrometry (MS).

Bruton's Tyrosine Kinase Inhibitors Prevent Therapeutic Escape in Breast Cancer Cells.

We have reported that a novel isoform of BTK (BTK-C) expressed in breast cancer protects these cells from apoptosis. In this study, we show that recently developed inhibitors of BTK, such as ibrutinib (PCI-32765), AVL-292, and CGI-1746, reduce breast cancer cell survival and prevent drug-resistant clones from arising. Ibrutinib treatment impacts HER2(+) breast cancer cell viability at lower concentrations than the established breast cancer therapeutic lapatinib.

Stromal-Based Signatures for the Classification of Gastric Cancer.

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies.

ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance.

ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent.

Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer.

Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors.

Emerging understanding of multiscale tumor heterogeneity.

Cancer is a multifaceted disease characterized by heterogeneous genetic alterations and cellular metabolism, at the organ, tissue, and cellular level. Key features of cancer heterogeneity are summarized by 10 acquired capabilities, which govern malignant transformation and progression of invasive tumors. The relative contribution of these hallmark features to the disease process varies between cancers.

Autofluorescence removal using a customized filter set.

Quantitative fluorescence microscopy is severely hindered by intrinsic autofluorescence (AF). Endogenous fluorescent molecules in tissue and cell samples emit fluorescence that often dominates signals from specific dyes. This makes AF removal critical to the development and practice of quantitative fluorescence microscopy.

Lipid biology of breast cancer.

Alterations in lipid metabolism have been reported in many types of cancer. Lipids have been implicated in the regulation of proliferation, differentiation, apoptosis, inflammation, autophagy, motility and membrane homeostasis. It is required that their biosynthesis is tightly regulated to ensure homeostasis and to prevent unnecessary energy expenditure.

Multiplexed analysis of proteins in tissue using multispectral fluorescence imaging.

We present a new application of multispectral analysis for subcellular measurement of multiple proteins in formalin-fixed paraffin embedded tissue and cells. Typically, the targets of interest are present in the same or spatially overlapping cellular compartments. Such co-localization can complicate analysis and interpretation of the images obtained using traditional fluorescence, especially when spectrally overlapping labels are present.