A proteomic screen was used to hierarchize candidate protein biomarkers involved in mesothelioma tumorigenesis in 22 preneoplastic (included in groups G1 and G2) and 4 neoplastic mesothelial cell lines (group G3) (Figure 1), established in immunocompetent rats after intraperitoneal induction with asbestos fibers. Another objective was to identify biomarkers of mesothelioma invasiveness, and/or the epithelial-to-mesenchymal transition (EMT) distinguishing preneoplastic cell lines with sarcomatoid (G2, n = 12) or epithelioid (G1, n = 10) morphology (Figure 2). 200 nanograms of each cell line’s protein lysates were trypsin-digested. Resulting peptides were analyzed at the Prot’ICO platform by LC-MS/MS with a nanoHPLC hyphenated with a TIMS-TOF Pro2. Data were acquired in dia-PASEF mode and quantitatively analyzed. Proteins bearing Q-values <1% FDR for differential expression between the compared phenotypic groups were submitted to Ingenuity Pathway Analysis® (IPA) at Cochin Institute for over-representation analysis and activation status prediction.