On August 9, 2022 NanoString Technologies, Inc. (NASDAQ: NSTG), a leading provider of life science tools for discovery and translational research, reported a peer-reviewed paper published in Nature Genetics using the GeoMx Human Whole Transcriptome Atlas (WTA) to construct a high-resolution molecular landscape of pancreatic cancer (Press release, NanoString Technologies, AUG 9, 2022, View Source [SID1234617956]). This paper, along with a tissue image generated using the GeoMx Digital Spatial Profiler (DSP), is featured on the cover of the August 2022 edition of Nature Genetics.
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The paper, "Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment," was authored by a team led by William L. Hwang, M.D., Ph.D., Assistant Professor at Harvard Medical School and Clinician-Investigator in the Center for Systems Biology, Center for Cancer Research and Department of Radiation Oncology at Massachusetts General Hospital.
Since pancreatic cancer is one of the most challenging malignancies to treat with standard approaches, the research team sought to advance precision oncology strategies by understanding the molecular landscape of the multicellular subtypes and spatial communities of this cancer, including how they are remodeled after treatment.
The researchers used single-nucleus RNA sequencing (snRNA-seq) and digital spatial profiling with the GeoMx WTA to profile the tumors from a cohort of patients before or after neoadjuvant intervention. The snRNA-seq cell type signatures were used to deconvolve the GeoMx spatial profiles, demonstrating the complementarity of the two platforms. Together, the platforms demonstrated that malignant cells following different cellular programs (basal-like vs. classical-like) cluster in distinct immune niches within a tumor. The spatially-resolved transcriptomics analysis supported the hypothesis that basal-like malignant cell programs and classical-like programs drive different degrees of immune infiltration with distinct immune cell compositions and suggests that therapeutic strategies may be more effective if differentially targeted for these specific phenotypes.
"Since resistance to cytotoxic therapy is pervasive, there is a critical need to elucidate clinically-relevant gene expression programs and spatial relationships among malignant and stromal cells in the tumor microenvironment, particularly in residual disease," said Hwang. "GeoMx spatial technology was critical in achieving this research objective because it allowed us to map our single-nucleus gene expression programs onto the tumor architecture with high fidelity (whole transcriptome) and in a cell-type specific manner (morphology antibody-based segmentation) and was optimized for FFPE samples, which is the specimen format that is most commonly available in the clinic. This unique combination of technological features enabled us to refine our understanding of the molecular taxonomy and spatial organization of PDAC that will ultimately advance precision oncology for this deadly disease."
The high-resolution molecular framework sheds light on pancreatic cancer’s inter-and intra-tumoral diversity, spatial organization into discrete communities, treatment-associated remodeling, and clinically relevant prognostication. With these findings, researchers can harness this information to augment precision oncology efforts in pancreatic cancer and drive significant breakthroughs in oncology research.