Uncovering Differently Expressed Markers and Heterogeneity on Human Pancreatic Cancer

Abstract

Discovery of biomarkers is critical to understand tumor heterogeneity and microenvironment. To determine differently expressed makers on cancer tissue for comprehensive profiling, the multiplexed tissue imaging mass cytometer (IMC) which uniquely combines time-of-flight mass spectrometry with metal-labeling technology to enable breakthrough discovery on single cell level was employed to investigate the expression of seven markers related to the epithelial-to-mesenchymal transition [α-smooth muscle actin (α-SMA), vimentin, collagen I, cytokeratin 7, pan-keratin], tumor proliferation (Ki-67), and human leucocyte antigen (HLA-DR) on human pancreatic cancer tissue. The difference was analyzed using bioinformatic tools. We observed the high expression of α-SMA, vimentin, collagen I, and Ki-67 on grade I but not on grade III. HLA-DR was highly expressed on grade I/III but not on grade II. Overall, the expression of markers has elucidated the heterogeneity intratumors. Additionally, to identify biomarkers on pancreatic cancer cells by blind systematic evolution of ligands by exponential enrichment (SELEX), aptamer pull-down assay and liquid chromatography–tandem mass spectrometry were used. Mortalin was identified as a potential a prognostic marker of pancreatic cancer. Our studies demonstrate that the IMC and blind SELEX might be implemented to discover biomarkers which can be used to better understand tumor biology and biomedical research applications.