Dataset Information

Peptidome profiling of ovarian cancer and non-cancer proximal fluids: ascites and blood sera

ABSTRACT: Ovarian cancer is the most lethal gynecological malignancy, because its early detection is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. Despite a large number of proteomic studies of biological fluids from ovarian cancer patients, only a few biomarkers are used in clinical practice. Low molecular weight endogenous peptides more easily diffuse across endothelial barriers and can be more relevant biomarker candidates. In this current study, detailed peptidomic analysis of 26 ovarian cancer and 15 non-cancer samples of biological fluids (ascites and sera) were performed using TripleTOF 5600+ mass-spectrometer.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum, Ascites

DISEASE(S): Cirrhosis,Disease Free,Malignant Neoplasm Of Ovary

SUBMITTER: Georgij Arapidi

LAB HEAD: Georgij Arapidi

PROVIDER: PXD009382 | Pride | 2018-04-05

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	N173-20130816_SWP-2_Q1_noHeat_120minGrad_7ulinj_IDA_200Th_1.wiff	Wiff
	N173-20130816_SWP-2_Q1_noHeat_120minGrad_7ulinj_IDA_200Th_1.wiff.scan	Wiff
	N173.group	Other
	N173_MGFPeaklist.dat	Other
	N173_MGFPeaklist.mgf	Mgf

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Publications

Peptidome profiling dataset of ovarian cancer and non-cancer proximal fluids: Ascites and blood sera.

Shender Victoria V Arapidi Georgij G Butenko Ivan I Anikanov Nikolay N Ivanova Olga O Govorun Vadim V

Data in brief 20181219

Despite a large number of proteomic studies of biological fluids from ovarian cancer patients, there is a lack of sensitive screening methods in clinical practice (Kim et al., 2016) (DOI:https://doi.org/10.1111/cas.12987[1]). Low molecular weight endogenous peptides more easily diffuse across endothelial barriers than proteins and can be more relevant biomarker candidates (Meo et al., 2016) (DOI:https://doi.org/10.18632/oncotarget.8931[2], (Bery et al., 2014) DOI:https://doi.org/10.1186/1559-027 ...[more]

PMID: 30627607

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Project description:Background: Transcoelomic spread is the major route of metastasis of ovarian high-grade serous carcinoma (HGSC) with the omentum as the major metastatic site. Its unique tumor microenvironment with its large populations of adipocytes, mesothelial cells and immune cells establishes an intercellular signaling network that is instrumental for metastatic growth yet poorly understood. Methods: Based on transcriptomic analysis of tumor cells, tumor-associated immune and stroma cells we defined intercellular signaling pathways for 284 cytokines and growth factors and their cognate receptors after bioinformatic adjustment for contaminating cell types. The significance of individual components of this network was validated by analyzing clinical correlations and potentially pro-metastatic functions, including tumor cell migration, pro-inflammatory signal transduction and TAM expansion. Results: The data show an unexpected prominent role of host cells, and in particular of omental adipocytes, mesothelial cells and fibroblasts (CAF), in sustaining this signaling network. These cells, rather than tumor cells, are the major source of most cytokines and growth factors in the omental microenvironment (n=176 versus n=13). Many of these factors target tumor cells, are linked to metastasis and are associated with a short survival. Likewise, tumor stroma cells play a major role in both extracellular-matrix-triggered and lipid-mediated signaling. We have verified the functional significance of our observations for three exemplary instances. We show that the omental microenvironment (i) stimulates tumor cell migration via WNT4 which is highly expressed by CAF; (ii) induces pro-tumorigenic TAM proliferation in conjunction with high CSF1 expression by omental stroma cells and (iii) triggers pro-inflammatory signaling, at least in part via a HSP70 – NFkB pathway. Conclusions: The intercellular signaling network of omental metastases is majorly dependent on factors secreted by immune and stroma cells to provide an environment that supports ovarian HGSC progression. Clinically relevant pathways within this network represent novel options for therapeutic intervention.

Project description:Ovarian cancer is a major cause of cancer mortality among women largely due to late diagnosis of advanced stage metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins particularly associated with metastatic disease so that we can better understand the metastatic process and identify potential therapeutic targets. Proteins are the target of many recently developed cancer treatments, but an often neglected aspect of biomarker discovery is protein glycosylation, especially those involving tumor-associated carbohydrate antigens (TACAs) such as sialyl-Lewis(x) (SLe(x) and sialyl-Lewis(a) (SLe(a), which have been identified in various cancers. Although it is already known that considerable changes in protein glycosylation are major contributors to the initiation, progression and metastasis of tumors, specifics about glycosylation changes particularly important to the metastatic process are still lacking. In this report we describe the results of a combined glycomic and proteomic study of metastatic ovarian cancer (OC) ascites fluids. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices. Separate glycomic and proteomic analyses were performed as well as glycopeptide analyses. Relative abundances of different N-glycan groups and proteins were identified from original ascites fluids and corresponding lectin bound samples. Levels of biomarkers CA125, MUC1 and fibronectin were also monitored in these samples by Western blot analysis. N-glycan analysis of ascites fluids showed the presence of large, highly fucosylated and sialylated, complex and hybrid glycans, some of which were not observed in normal serum. Proteins in OC ascites that were more abundant or not present in the serum control, were haptoglobin, fibronectin, lumican, fibulin, hemopexin, ceruloplasmin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Glycopeptide analysis identified N- and O-glycans in clusterin, hemopexin, and fibulin that were present in OC ascites.