Animal models have been widely used for experimentation and the mouse is a signature organism that is present in many labs. In this project, we will learn about the technological advances that allow us to improve the animal models in ways that enable discovery of biomarkers that could be more relevant to a disease detected in humans.
In a PDX model, a human tumor sample is implanted into immune-deficient mice, and human stroma is generally replaced by mouse stroma. Recently it was recognized that this approach also provides a simple and reliable method for separation of tumor and stroma expression profiles. The completeness of replacement can be evaluated by measuring the expression levels of human stromal markers, such as CAF markers fibroblast activation protein alpha (FAP) and chondroitin sulfate proteoglycan 4 (CSPG4). Thus, sequencing PDX-samples and measuring expression level of genes we can consider positively expressed human genes as genes expressed in tumor cells, and positively expressed mouse genes as genes expressed in stroma cells. These types of studies have their own limitations, but allow extensive characterization of human or even a specific patient tissue behavior in a lab environment.
This is an exciting project for those interested in translational research and biomarker use in cancer subtype characterization and associated technical skills needed to properly process data, eliminate technical issues and use machine learning tools to extract meaningful insights from complex molecular datasets.
Tumor Microenvironment – extracellular matrix, immune system and tumor cells: In the tumour microenvironment, cancer cells directly interact with both the immune system and the stroma. It is firmly established that the immune system, historically believed to be a major part of the body’s defence against tumour progression, can be reprogrammed by tumour cells to be ineffective, inactivated, or even acquire tumour promoting phenotypes. Likewise, stromal cells and extracellular matrix can also have pro- and anti-tumour properties.
Associated Publication and dataset:
Based on the publication “Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers,” James R. Bradford et. al.; DOI: 10.18632/oncotarget.8014. The dataset contains a total of 79 PDX samples: 37 lung and 19 breast cancer samples. These represent multiple cancer types (19 x breast, 37 x lung, 8 x colorectal, 7 x ovarian, 3 x endometrial, 2 x pancreatic, 2 x ampullary, 1 x leukaemia). http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3980/
Coming Soon !!!