2024 Theses Doctoral

Mass spectrometry-based proteomics as a tool to elucidate global changes in pancreatic ductal adenocarcinoma metastasis

Tang, Lauren Clarissa

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, with a five-year survival rate of only 13%. Patients are most commonly diagnosed in late stages, once the tumor has metastasized to distal organs, limiting treatment options. For PDAC patients, metastases most often go to the liver. However, there has been limited studies profiling matching human primary tumors and liver metastases because of the difficulty in procuring such samples.

To understand the system in which primary tumors spread to the liver, an omics approach is most appropriate. Proteins are the final effectors of the cell, making mass spectrometry-based proteomics an extremely useful tool in understanding the metastatic landscape of PDAC. Here, we present a novel study that offers a comprehensive proteomic characterization of matching human primary PDAC tumors and liver metastases. Using mass spectrometry-based proteomics, we were able to elucidate immune signatures on both the global proteomic and phosphoproteomic level in PDAC, as well as. In addition, this work can serve as a useful resource to the community to help generate more hypotheses and follow-up experiments.

Finally, we demonstrate the versatility and potential of mass spectrometry as a tool to probe various biological systems by offering a systematic comparison of the two main mass spectrometry acquisition types used in bottom-up proteomics. We found that data-dependent acquisition (DDA) and data-independent acquisition (DIA) can produce comparable results. However, DDA, in combination with isobaric labeling, disproportionally suffers from ratio compression, and DIA’s incompatibility with isobaric labeling for multiplexing can be a big drawback when working with limited sample amounts.