RESUMO
Proteins of the pregnancy specific ß-1 glycoprotein (PSG) family are renowned for their elevated expression during pregnancy. Only few reports have investigated their expression in adenocarcinomas. We studied the expression of PSG1 in pancreatic adenocarcinoma (PDAC). In a cohort of 104 patient samples, immunohistochemical analysis determined PSG1 expression in every specimen. PSG1 was found at apical and cytoplasmic localization or solely at cytoplasmic localization, with the latter case being correlated to shortened median survival (25 vs 11 months, logrank p-value < 0.001). At the same time, enzyme linked immunosorbent assay (ELISA) did not detect elevated PSG1 levels in the plasma of PDAC patients as opposed to the plasma of healthy, non-pregnant control individuals. We also probed the impact of PSG1 expression in a murine tumor model system, using subcutaneous injection of Colo-26 cells into immunocompetent BALB/c mice. Here, tumor growth was not affected by the expression of human PSG1. Our study reaffirms interest into the tumor-contextual biology of PSG proteins.
RESUMO
PURPOSE: FFPE (formalin fixed, paraffin embedded) tissue cohorts represent an enduring archive of clinical specimens. Proteomic analysis of FFPE tissues is gaining interest for the in-depth analysis of aberrant proteome composition. Procedures for FFPE tissue processing are standardized but there is diversity regarding the different processing systems. This work focuses on three different processing methods commonly used in large European pathology institutes. EXPERIMENTAL DESIGN: Formalin fixed tissue specimens of different tumors were serially sliced and processed with three different processing systems (xylene, ethanol/vacuum or microwave based). After paraffin embedding, they were subjected to MS-based proteomic analysis to investigate the impact of tissue processing techniques on the quality of proteomic analysis. Results were compared with proteomic analysis of corresponding cryopreserved tissue specimens. RESULTS: All processing techniques achieved very good proteome coverage similar to the cryopreserved counterpart. Gene ontology profiles, relative protein abundances, and peptide modifications such as methionine oxidation or proteolytic truncation were highly similar for all techniques as well as for the cryopreserved samples. CONCLUSIONS AND CLINICAL RELEVANCE: The results show that different processing procedures do not impede proteomic analysis as a robust and powerful approach for the identification of protein determinants and markers of disease processes and highlights the general robustness of FFPE-tissue based proteomics.
