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Malignant mesothelioma (MM) still represents a devastating disease that is often detected too late, while the current effect of therapies on patient outcomes remains unsatisfactory. Invasiveness biomarkers may contribute to improving early diagnosis, prognosis, and treatment for patients, a task that could benefit from the development of high-throughput proteomics. To limit potential sources of bias when identifying such biomarkers, we conducted cross-species proteomic analyzes on three different MM sources. Data were collected firstly from two human MM cell lines, secondly from rat MM tumors of increasing invasiveness grown in immunocompetent rats and human MM tumors grown in immunodeficient mice, and thirdly from paraffin-embedded sections of patient MM tumors of the epithelioid and sarcomatoid subtypes. Our investigations identified three major invasiveness biomarkers common to the three tumor sources, CAPG, FABP4, and LAMB2, and an additional set of 25 candidate biomarkers shared by rat and patient tumors. Comparing the data to proteomic analyzes of preneoplastic and neoplastic rat mesothelial cell lines revealed the additional role of SBP1 in the carcinogenic process. These observations could provide new opportunities to identify highly vulnerable MM patients with poor survival outcomes, thereby improving the success of current and future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis. [ABSTRACT FROM AUTHOR]