Dataset Information

Biomarkers discovery for Colorectal cancer

ABSTRACT: Identification of early diagnostic and prognostic biomarkers measurable in liquid biopsies remains a major challenge in oncology today. OMICs technologies cannot be applied on clinically precious human material as this is required in its integrity for routine pathology investigation. Hence all OMICs discovery today is done on residual and not clinically relevant material. In the study, we present a novel, non-destructive, procedure named EXPEL, which uses rapid, pressure-assisted, interstitial fluid extrusion, allowing for full clinical pathology and OMICs analysis (proteins, metabolites, miRNA and DNA) on the same specimen. To demonstrate this we engage in a simultaneous biomarker discovery and routine diagnostic analysis of human colorectal cancer and liver metastases. Biomarkers discovered with EXPEL methodology can be readily detected in human sera, allowing for unprecedented translation to the clinic. EXPEL method enables for the first time both clinicians and scientist to explore identical, fresh, clinical material regardless of origin and size.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: Dominique Baiwir

LAB HEAD: Vincent Castronovo

PROVIDER: PXD005693 | Pride | 2018-10-26

REPOSITORIES: Pride

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Publications

Innovative methodology for the identification of soluble biomarkers in fresh tissues.

Costanza Brunella B Turtoi Andrei A Bellahcène Akeila A Hirano Touko T Peulen Olivier O Blomme Arnaud A Hennequière Vincent V Mutijima Eugene E Boniver Jacques J Meuwis Marie-Alice MA Josse Claire C Koopmansch Benjamin B Segers Karin K Yokobori Takehiko T Fahmy Karim K Thiry Marc M Coimbra Carla C Garbacki Nancy N Colige Alain A Baiwir Dominique D Bours Vincent V Louis Edouard E Detry Olivier O Delvenne Philippe P Nishiyama Masahiko M Castronovo Vincent V

Oncotarget 20180131 12

The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure ...[more]

PMID: 29535834

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Project description:Background Loss of skeletal muscle mass in advanced cancer is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are still lacking. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in muscle proteome and secretome associated with cancer-induced cachexia to better understand cellular mechanisms involved in this wasting process and to identify secreted proteins which might reflect the ongoing muscle atrophy process. Methods We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Selected reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Their muscle source was demonstrated by assessing their gene expression in skeletal muscle and in cultured myotubes. Finally, we also investigated their regulation in muscle cells. Alterations in several molecular pathways potentially involved in muscle atrophy were highlighted using Gene ontology enrichment analyses. Results Our results revealed a dramatic increased production (2-to 25-fold) by the muscle of several acute phase reactants (APR: Haptoglobin, Serpina3n, Complement C3, Serum amyloid A1) which are also released in the circulation during C26 cancer cachexia. Their production was confirmed in other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Glucocorticoids and pro-inflammatory cytokines contribute directly to their increased expression in muscle cells in vitro, while the role of IL-6 in the muscular induction of these APR was demonstrated in vivo. Conclusions Cancer is associated with marked changes in muscle secretome during muscle wasting. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.

Dataset Information

Biomarkers discovery for Colorectal cancer

Publications

Innovative methodology for the identification of soluble biomarkers in fresh tissues.

Similar Datasets

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