Microgenomics 2021 webinar : Tissue spatially resolved molecular profiling for personalized oncology
Channel: The International Symposium on Microgenomics 2023
Date: 2021-11-04

Dr Lance Liotta is cofounder  and coDirector of the Center for Applied Proteomics and Molecular Medicine at Geoprge Mason University, USA where he is also Medical Director of the Clinical Proteomics Laboratory. Dr. Liotta has devoted his career to the study of tumor invasion and metastis and the creation of technology for molecular analysis of tissue and body fluids. This technology includes Laser Capture Microdissection, Reverse Phase Protein Microarrays, Biomarker Harvesting Hydrogel Nanoparticles and Molecular Preservatives for Phosphoprotein Preservation. 


The future of molecular oncology is personalized therapies guided by molecular profiling of the patient’s tumor. Ten years ago oncology diagnostics faced the reality of tumor heterogeneity at the level of genomics, proteomics, and the tissue cellular microenvironment.  At the molecular and cellular level each patient’s tumor is unique. Addressing this challenge, over the past five years, there has been an explosion in specialized technology for spatially resolved molecular profiling of tumor tissue.

Recognition of the limitations of whole-tissue extraction profiling has driven a rapidly expanding field of investigators who are creating technology, software, and analytical tools to explore the tissue cellular spatial interactome. Consequently, a rich set of new research tools now exists to histologically localize proteomic and genomic markers, or to physically procure subpopulations of cells, or individual cells, within a formalin fixed or frozen section. Within this cadre of technologies Laser Capture Microdissection (LCM), CyTOF, NanoString, Geo-Seq, tomo-Seq, TIVA, smFISH, RNAscope, SeqFISH, VISIUM, LCseq, Scanning MALDI, and a host of others, has proven to be a reliable means of procuring tissue cellular populations, achieving high sensitivity and high precision for multiplex genomic and proteomic profiling. Post translational modifications such as protein phosphorylation provide key functional information that cannot be obtained by genomic and transcriptomic profiling. Now we are seeing the transition of tumor tissue spatial profiling from the research lab to clinical trial validation of tissue cellular genomic (mRNA, NGS), proteomic, and phosphoprotein signal pathway quantitation, as strategies to guide patient therapy.

Genomic profiling of whole tissue specimens has shown considerable clinical potential for the classification of patient responses to chemotherapy. Nevertheless extracting a whole tissue specimen is associated with a very high degree of preanalytical variability due to cellular heterogeneity, the unknown proportion of tumor or host subpopulations that all contribute to the extract, and the destruction of information about the spatial location of cell types within the tissue. For a variety of molecular targeted therapies, an RNA transcript related to the molecular drug target can be expressed in tumor cells as well as non-tumor host stroma and immune cells. The need for spatial molecular mapping is particularly important in tumor immunology, and tumor sub-clonal analysis, where the spatial proximity (and class) of tumor cell and immune cell populations provides critical information relevant to immunotherapy and drug resistance phenotypes. Thus, the ideal tissue spatial profiling technology should permit genomic, and proteomic functional analysis of the same cells or cellular subpopulations while retaining their spatial context. The major area of emphasis for this Special Session is the exciting rapidly emerging frontier of tissue single cell molecular analysis that combines proteomics with genomic, and transcriptomic analysis.

We  envisage near-term future workflows for the technology in which a diagnostic biopsy pathologic tissue section histologic image is digitally captured at high resolution, sent to the cloud, and then marked up remotely on a scientist or clinician’s computer screen. Once the specific histopathology regions are marked for interrogation on-screen (including groups of cells, single cells, immune cells, stromal cells etc.), these regions are automatically and remotely microdissected by LCM, followed by proteomic, genome sequencing and mRNA transcriptomic evaluation. The data from the molecular analysis of each selected region is then ported back through the cloud and can be viewed on-screen as a separate laboratory report for each individual histologic region that is highlighted, for integrated clinical and molecular data analysis.