Dataset Information

S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.

ABSTRACT: 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.

SUBMITTER: Nader JS

PROVIDER: S-EPMC7226589 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.

Nader Joëlle S JS Guillon Jordan J Petit Coralie C Boissard Alice A Franconi Florence F Blandin Stéphanie S Lambot Sylvia S Grégoire Marc M Verrièle Véronique V Nawrocki-Raby Béatrice B Birembaut Philippe P Coqueret Olivier O Guette Catherine C Pouliquen Daniel L DL

Cancers 20200410 4

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 n ...[more]

PMID: 32290283

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Project description:ObjectivesPrognostic models for malignant pleural mesothelioma (MPM) are needed to prevent potentially futile outcomes. We combined MPM plasma biomarkers with validated clinical prognostic indices to determine whether stratification of risk for death in 194 patients with MPM improved.MethodsIndividuals were recruited from three different centers: a discovery cohort (83 patients with MPM) created by combining patients from two U.S. centers and a separate, independent cohort from Canada (111 patients with MPM). Univariable and multivariable analyses were performed on the initial discovery and independent cohorts separately. In the multivariable analyses, prognostic factors were adjusted for the European Organisation for Research and Treatment of Cancer (EORTC) prognostic index (PI) of mesothelioma. The prognostic significance of adding plasma biomarker data to the PI was determined by using the likelihood ratio test, comparing models with and without the addition of biomarker to the clinical PI. The predictive ability of the biomarker was then assessed formally using Harrell's C-index by applying the fitted model variables of the discovery cohort to the second, independent cohort, including and not including the biomarker with the PI.ResultsHigher levels of osteopontin and mesothelin were individually associated with worse prognosis after adjusting for the PI. In the independent cohort, incorporating either plasma osteopontin or mesothelin into the baseline predictive PI model substantively and statistically significantly improved Harrell's C-statistic. In the final prognostic model, log-osteopontin, EORTC clinical prognostic index, and hemoglobin remained as independently significant predictors and the entire prognostic model improved the optimism-corrected Harrell's C-index significantly, from 0.718 (0.67-0.77) to 0.801 (0.77-0.84).ConclusionsThese data suggest a possible role for preoperative plasma biomarkers to improve the prognostic capability of the EORTC PI of MPM.

Dataset Information

S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.

Publications

S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.

Similar Datasets

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