Abstract
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.
Highlights
The management of malignant mesothelioma (MM) remains a challenge today given its complex biology and aggressiveness, and the absence of specific early symptoms [1]
The four rat MM tumor models shared a sarcomatoid morphology of tumor cells but differed in their infiltrative potential
We investigated whether some of the 28 candidate biomarkers common to the rat and human MM (Figure 2D) exhibited additional abundance changes during the carcinogenesis process
Summary
The management of malignant mesothelioma (MM) remains a challenge today given its complex biology and aggressiveness, and the absence of specific early symptoms [1]. The effect of current and new therapies on overall survival remains very modest [2], prompting the need to search for biomarkers that could improve early diagnosis, prognosis, and treatment [3]. Acquisition of all Theoretical Mass Spectra (SWATH-MS) has recently emerged as a promising new tool in cancer proteomics, making it possible to identify biomarkers of increasing stages of invasiveness in MM experimental models, for example [4]. Proteomic analyzes of MM have already provided lists of putative cancer biomarkers, significant differences are observed between primary and commercial MM cell lines [5], Cancers 2020, 12, 2430; doi:10.3390/cancers12092430 www.mdpi.com/journal/cancers. To recapitulate the spectrum of tumor heterogeneity seen in patients, and limit the impact of differences in stromal conditions observed between patient and cancer models, cross-species proteomic analyzes are suggested to improve preclinical evaluation [11] Long-established human cell lines [7], some genetically engineered mouse models [8], and subcutaneous xenograft models of human tumors [9,10] often fail to predict drug effects in clinical practice.
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