Proteomic surfaceome analysis of mesothelioma

Abstract

Identification of new markers for malignant pleural mesothelioma (MPM) is a challenging clinical need. Here, we propose a quantitative proteomics primary screen of the cell surface exposed MPM N-glycoproteins, which provides the basis for the development of new protein-based diagnostic assays. Using the antibody-independent mass-spectrometry based cell surface capturing (CSC) technology, we specifically investigated the N-glycosylated surfaceome of MPM towards the identification of protein-marker candidates discriminatory between MPM and lung adenocarcinoma (ADCA). Relative quantitative CSC analysis of MPM cell line ZL55 in comparison with ADCA cell line Calu-3 revealed a bird's eye view of their respective surfaceomes. In a secondary screen of fifteen MPM and six ADCA, we used high throughput low density microarrays (LDAs) to verify specificity and sensitivity of nineteen N-glycoproteins overregulated in the surfaceome of MPM. This proteo-transcriptomic approach revealed thy-1/CD90 (THY1) and teneurin-2 (ODZ2) as protein-marker candidates for the discrimination of MPM from ADCA. Thy-1/CD90 was further validated by immunohistochemistry on frozen tissue sections of MPM and ADCA samples. Together, we present a combined proteomic and transcriptomic approach enabling the relative quantitative identification and pre-clinical selection of new MPM marker candidates.

Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels

“…18,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Several identified SNPs were located in or near genes that might be involved in biological pathway leading to lung function impairment (ie, GALNT13 and PCDH9, respectively). GALNT13 belongs to the GalNAcT family of enzymes, which initiate O-glycosylation of mucins.…”

“…Recently, Teneurin-2 was shown to be expressed in the majority of malignant mesothelioma cell lines but not in lung adenocarcinoma cell lines investigated. 41,42 Mesothelioma is a rare form of cancer developing in the mesothelium, the protective body that covers many of the internal organs of the body, such as the pleura (the outer lining of the lungs and internal chest wall). Mesothelioma is most commonly caused by (occupational) exposure to asbestos.…”

Multiple roles of CD90 in cancer

“…In their study, they showed that CD90 was expressed only in the epithelioid mesothelioma (15 cases) but not in lung adenocarcinoma (61 cases) [84]. Similarly, proteomic surfaceome analysis of Nglycosylated protein in mesothelioma and lung adenocarcinoma also found CD90 to be expressed exclusively in malignant pleural mesothelioma cell lines (MSTO-211H, H2052, H2452, H226) but not in lung adenocarcinoma cell lines (Calu-3, A549, Calu-6, SK-LU-1) suggesting a role for CD90 as a diagnostic marker for mesothelioma [85]. In addition, CD90 was present along with other markers in the cells recovered from the primary xenograft of patient mesothelioma samples.…”

Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer

“…Using in silico analysis of transcriptomics data, we recently found evidence for altered expression of Ten-2 and Ten-4 in various tumor types [24], and expression of Ten-2 at the protein level has been detected in malignant pleural mesothelioma using a chemo-proteomic strategy [25]. Moreover, recurrent structural changes in the TENM3 gene have been identified in neuroblastoma, and low Ten-3 mRNA levels in these tumors were associated with shorter patient survival [26].…”