Recently, one of the early adopters of the Digital Spatial Profiling (DSP) technology, Michael Davies, MD, PhD, the Deputy Chairman and Associate Professor in the Department of Melanoma Medical Oncology at the MD Anderson Cancer Center, shared some of his early data and impressions of the technology.
Dr. Davies and his team used the DSP platform to investigate protein signaling pathways and the anti-tumor immune response in heterogeneous melanoma tumors. The DSP platform eliminated the need to physically excise regions of interest (ROI) by microdissection from the formalin-fixed paraffin-embedded (FFPE) tissue, as is standard with traditional techniques. Marking the expression of the tumor-suppressor protein PTEN by immunohistochemistry (IHC), the group compared the multi-plex protein expression profile from ROIs selected from PTEN-positive and PTEN-null regions within a tumor with heterogeneous expression. Consistent with previous studies in tumors with uniform expression, the DSP platform confirmed that regions within the tumors with complete loss of PTEN had increased levels of phospho-AKT (P-AKT) compared to the regions with intact PTEN. In addition to providing important validation of previous studies and the significance of intratumoral heterogeneity, for the first time the group could also appreciate spatial heterogeneity within the PTEN-null regions. Because of the speed of sample processing and data collection with DSP, they were able to analyze several such tumors with heterogeneous PTEN expression, identifying significant differences in key signaling proteins and immune cell markers.
Dr. Davies’ team also applied the DSP platform to analyze signaling pathways in surgically resected brain metastases and extracranial metastases from metastatic melanoma patients. The DSP platform again facilitated their ability to efficiently analyze multiple selected regions in these heterogeneous specimens to characterize molecular differences between melanoma cells growing in the brain and other metastatic sites. In addition to validating previously seen molecular differences in brain metastases and extracranial metastases, the DSP analysis provided new information about the spatial heterogeneity of the molecular features within each tumor. In a pilot study, RNA expression was also assessed with DSP and again provided novel insights into the spatial heterogeneity of gene expression patterns within tumors. Studies are ongoing to integrate data from these different molecular platforms to further understand the dynamics of signaling pathways and the immune response within the tumor microenvironment.
Combining multi-parameter molecular analysis, spatial resolution, and high speed, quantitative analysis of samples is poised to revolutionize the field of immuno-oncology. Scientists will be able to better understand disease progression and identify molecular drivers within the tumor and the host immune response. Because the DSP platform is compatible with FFPE samples and nondestructive, whole archives of specimens once only examined by H&E staining can now be quickly and efficiently reevaluated with hundreds or thousands of analytes. The possibilities and potential experiments are boundless; finally scientists have a technology that can keep up with their imagination.
To learn more about Dr. Davies’ study, watch Integrated Interrogation of Oncogenic Signaling Pathways, Immunology, and Heterogeneity in Cancer
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Digital Spatial Profiling is for research use only. It is not for use in diagnostic procedures.