MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/x01/MSV000083385/primaryOK2000000Christopher Gernerhttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=6ed851781bd140c6900a6cdd855c65cdchristopher.gerner@univie.ac.atMassIVE38UNIMOD:4 - "Iodoacetamide derivative."MOD:00894UNIMOD:1 - "Acetylation."UNIMOD:35 - "Oxidation or Hydroxylation."ProteomicsQ ExactiveHomo Sapiens (ncbitaxon:9606)University of Vienna, Faculty of Chemistry, Department of Analytical ChemistryPathophysiologies of cancer-associated syndromes such as cachexia are poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA, and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting of nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44, and C4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics. Remarkably, these molecules are known to be involved in key processes of cancer cachexia. Based on these results, we propose a model how metastatic melanoma may lead to reprogramming of organ functions via formation of platelet activating factors from long-chain polyunsaturated phosphatidylcholines under oxidative conditions and via systemic induction of intracellular calcium mobilization. Calcium mobilization in platelets was demonstrated to alter levels of several of these marker molecules. Additionally, platelets from melanoma patients proved to be in a rather exhausted state, and platelet-derived eicosanoids implicated in tumor growth were found massively increased in blood from three melanoma patients. Platelets were thus identified as important source of serum protein and lipid alterations in late stage melanoma patients. As a result, the proposed model describes the crosstalk between lipolysis of fat tissue and muscle wasting mediated by oxidative stress, resulting in the metabolic deregulations characteristic for cachexia.Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma.Muqaku Besnik B, Eisinger Martin M, Meier Samuel M SM, Tahir Ammar A, Pukrop Tobias T, Haferkamp Sebastian S, Slany Astrid A, Reichle Albrecht A, Gerner Christopher Cprojections, BODYFAT, nucleocytoplasm, Surrogate Endpoints, Pgp-1, Laboratory, Aminoessigsaeure, Muscle hypotrophy, PGP-1, Gly, Choline phosphatide, Metabonomics, growth and development, Scc-1, hyaluronate receptor, BDPLT1, sci, Tumor, BDPLT3, MAGE-E1 antigen, protein polypeptide chains, Extracellular matrix receptor III, MSK16, Oxidative DNA, Oxidative, Biological, R-PTP-ETA, HOW, How, 1, 2, monocyte differentiation antigen CD14, Nitro-Oxidative Stresses, B8, DNA Damage, PGP-I, organ, DL-Asparagine, asparagina, G, D1S181E, Glycine, anabolism, N, L-Asparagine, Tissue, Oxidative Cleavage, stru, HEL-141, myeloid cell-specific leucine-rich glycoprotein, proteins, l(3)S053606, wasting - muscle, ch, Amyotrophy, decreased, Oxidative Stresses, MCSPG, HERMES, Glycocoll, Bpife, BET, release of stored calcium ion (Ca2+) into cytoplasm, stage, Phosphatidylcholine, cytoplasmic release of sequestered calcium ion (Ca2+), Hyaluronate receptor, OD107, intracellular, BPIFE, Tumors, Cobalt Salt Glycine, Viral, Epididymis luminal protein 141, Glycine Phosphate, GPIbA, CD44 antigen, Monosodium Salt Glycine, Malignant Melanomas, Copper Salt Glycine, multicellular organismal lipid catabolic process, DmIKKgamma, DmelCG7664, Benign, Marker, ly-24, dIKK, DAMAGE, Hepatocellular carcinoma-associated protein 1, shelf, GPIba, simple tissue, DNA Oxidative Damages, Acid, HUTCH-I, End Points, Glycine Sulfate (3:1), Glycerophospholipids, IKK-gamma, Benign Neoplasms, Immunologic, Cobalt Salt, 2-amino-3-carbamoylpropanoic acid, Laboratory Marker, projection, ridge, GPIb-alpha, Malignant Neoplasms, Nitro-Oxidative, polyunsaturated phosphatidylcholine, Muscular atrophy, Platelet, DNA, EPA, PTPbeta2, platelet, other neoplasm, GP1B, Aa1249, Oxidative Damage, CD42b-alpha, lipids, TIMP-1, EPO, Cysteine-rich protein 1, DBPLT3, Peptidomics, lamellae, Antioxidative, Clinical Marker, Neoplasms, developmental stage, 35F(AT)[[17]], Hasp, AI450271, biosynthesis, protein-containing complex, process of organ, dIKK-gamma, lamella, melanoma (disease), IN, CYRP, urinary form, DmIKK-gamma, 4732461B14Rik, Gene Products, Phosphatidyl, Oxidative Damages, portion of blood, Injury, Clinical, dysfunction, Naevocarcinoma, Monosodium Salt, AI847422, Ac1-114, synthesis, Neoplasias, l(2)k03505, Phagocytic glycoprotein I, CSPG8, anatomical unit, Antioxidative Stresses, 0610010I23Rik, body organ, bodyfat, AI255847, GPIbalpha, laminae, Thrombocyte, metastatic malignant melanoma, Biologic, Cancer, Malignant Neoplasm, 3-sn-Phosphatidylcholine, whole blood, Phagocytic glycoprotein 1, Monopotassium Salt Glycine, Serum Markers, Proteins, Copper Salt, Phosphatidyl Cholines, Phosphoglycerides, NG2, qkr, Anti-oxidative Stresses, l(3)S090417, Amyotrophy involving the extremities, Immune Marker, IKKgamma, AN2, MT, native protein, Surrogate End Point, Icosanoid, amyotrophia, Oxidative Nitrative Stresses, KH93F, Malignant Melanoma, chemical analysis, Neoplasm, Cholines, CD148, HCELL, organ process, Biologic Markers, Crp, CRP, primary cancer, Muscle wasting, Anti-oxidative Stress, Neurogenic muscular atrophy, DNA Oxidative Damage, RGD1560259, Surrogate, MS:35F.AT17, Dmikkgamma, increased number, extracellular matrix receptor III, Endpoints, bHLHe63, postnatal growth, Monopotassium Salt, Cancers, HMW-MAA, cytoplasmic release of stored calcium ion (Ca2+), Glyzin, enucleate thrombocyte, CG16910, 4-diamino-4-oxobutanoic acid, malignant tumor, Phosphatidyl Choline, Gene Proteins, processes, AP4, dAP-4, adipose, Ac2-069, Aminoacetic, Glykokoll, Stress, DBMT1, PC, Neoplasia, Calcium Salt, C77570, GP-Ib alpha, GP90 lymphocyte homing/adhesion receptor, Immune Markers, DNA Oxidative, Ly-24, Glycine Carbonate (2:1), Biological Markers, Viral Marker, HDLCQ9, AU023126, AP-4, Calcium Salt Glycine, determination, H2N-CH2-COOH, Epican, DEP-1, Blood, CD44A, postnatal development, Biochemical, Metabonomic, Endpoint, Nitrative Stress, Phosphatidyl-N-trimethylethanolamine, CG7664, protein, Monoammonium, Serum, Monosodium, Damage, element, BSS, Laboratory Markers, especially in the lower limbs, Thrombocytes, melanoma, Calcium Salt (2:1), Lymphocyte antigen 24, Nitro-Oxidative Stress, Monoammonium Salt Glycine, multicellular organism lipid catabolic process, gp300, protein aggregate, Oxidative Injury, fatty tissue, present in fewer numbers in organism, IKKg, l(3)j5D5, fat tissue, DEP1, Pgp1, KEY, Key, multicellular organismal biosynthetic process, 24B, increased, single-organism biosynthetic process, Lecithin, Oxidative Injuries, antigen CD42b-alpha, adipose system, CD42B, long, AW743261, Phosphate, release of sequestered calcium ion into cytoplasm, MCSP, LHR, Oxidative DNA Damages, Estimated, CD14, CG10293, heparan sulfate proteoglycan, ASN, Asn, Anti-oxidative, l(3)j5B5, Oxidative Stress Injuries, Immune, Markers, anucleate thrombocyte, malignant neoplasm, HCA1, Viral Markers, CD42b, papilla, muscle wasting, MDU2, MDU3, Malignancies, associated, METAA, 0904/17, Surrogate Endpoint, PLATEST, Icosanoids, CRP4, CRP2, CRP1, lamina, Blood Platelet, MC56, flanges, Neurogenic muscle atrophy, late, Biochemical Markers, Blood Serum, aminoethanoic acid, Biologic Marker, hermes antigen, results, Multiple Reaction Monitoring, GP90 lymphocyte homing|adhesion receptor, AW146109, Hermes antigen, Body Fat, Melanoma, GP1BA, SZ1, Oxidative and Nitrosative Stress, neurogenic, Wasting syndrome, Lipid, HCI, Kenny, CSRP, crp.4a, metastatic melanoma, internal to cell, SCC1, Scc1, CD44, Ab1-341, CDW44, l(2)00232, MIC4, growth pattern, non-developmental growth, Hgly, shelves, Byp, Timp, Muscle atrophy, Crpd, CDw44, DmelCG16910, Patient, Biochemical Marker, ECMR-III, blood platelet, anon-EST:Liang-2.39, Oxidative Stress Injury, RPTPJ, Wasting syndrome., mMage-e1, Platelets, accessory, TIMP, AW121933, Ba2-693, CIB8, Oxidative Stress, CRP-[a], Sodium Hydrogen Carbonate, Clinical Markers, Clgi, Lecithol, P62, RHAMM, Monopotassium, Benign Neoplasm, Antioxidative Stress, Gene, CLGI, l(2)35Fd, fat, Malignant, supernumerary, Monocyte differentiation antigen CD14, Surrogate End Points, Stresses, Lipolyses, Surrogate Markers, VWDP, l(2)SH1614, Oxidative Nitrative, reduced, polypeptide chain, Stress Injury, subnumerary, ESP1, thrombocyte, l(2)k00809, Oxidative Cleavages, Glycine Hydrochloride (2:1), dmIKKgamma, Metabolomic, IKK[[gamma]], Choline Glycerophospholipids, protoplasm, Ptpb2, Biomarker, calcium mobilization, epican, Glycine Hydrochloride, l(3)s2612, MRM, protoplast, Malignancy, formation, Biological Marker, phagocytic glycoprotein I, ridges, decreased number, Asparagin, release of stored calcium ion (Ca2+), Immunologic Markers, Muscle degeneration, CRP-[b], Salt Glycine, Glycin, phagocytic glycoprotein 1, IKK, Anti oxidative Stress, p80, phosphatidylcholines, Oxidative DNA Damage, Clients, DmelCG10293, Phospholutein, Leimzucker, 2-aminoacetic acid, Choline, Immunologic Marker, BG:DS02740.3, Monoammonium Salt, calcium ion (Ca2+) mobilization, Glycine Phosphate (1:1), HPTPeta, ptx1, clone 2.39, protein complex, malignant, vertebrate blood, Alpha-dystrobrevin-associated MAGE Protein, Aminoacetic acid, End Point, Eicosanoid, Client, Heparan sulfate proteoglycan, development, Melanomas, Oxidative Nitrative Stress, Glycine Carbonate (1:1), natural protein, Ac1262, Myeloid cell-specific leucine-rich glycoprotein, Protein, Hydrochloride, membrane-bound form, SAA, flange, 2-Diacyl-sn-glycero-3-phosphocholine, who, Aminoacetic Acid, Serum Marker, Hlp, glycoprotein Ibalpha, l(2)SH2 1614, pathophysiology, Ab2-196, Who/How, Monolithium Salt, release of sequestered calcium ion (Ca2+), Cleavage, Choline Phosphoglycerides, Surrogate Marker, Protein Gene Products, lymphocyte antigen 24, present in greater numbers in organism, fatty depot, qkr[93F], MEL-CSPG, malignant melanoma, assay, PTX1, Nitro Oxidative Stress, growth, Serumsprojections, BODYFAT, nucleocytoplasm, Surrogate Endpoints, syndrome associated with disease or disorder, Pgp-1, Laboratory, Aminoessigsaeure, Muscle hypotrophy, PGP-1, Gly, Choline phosphatide, Metabonomics, growth and development, Scc-1, hyaluronate receptor, BDPLT1, sci, Tumor, BDPLT3, MAGE-E1 antigen, Extracellular matrix receptor III, MSK16, Oxidative DNA, Oxidative, Biological, C4AD, R-PTP-ETA, HOW, How, 1, 2, monocyte differentiation antigen CD14, Nitro-Oxidative Stresses, B8, C4A6, C4A4, DNA Damage, C4A3, PGP-I, C4A2, organ, DL-Asparagine, asparagina, molecules, G, D1S181E, Glycine, anabolism, N, L-Asparagine, Tissue, C4, Oxidative Cleavage, stru, HEL-141, myeloid cell-specific leucine-rich glycoprotein, Molekuel, l(3)S053606, wasting - muscle, Amyotrophy, Oxidative Stresses, MCSPG, HERMES, Glycocoll, Bpife, Symptom Clusters, BET, release of stored calcium ion (Ca2+) into cytoplasm, Blood Protein, stage, Phosphatidylcholine, cytoplasmic release of sequestered calcium ion (Ca2+), Hyaluronate receptor, OD107, intracellular, BPIFE, Tumors, Cobalt Salt Glycine, Viral, Epididymis luminal protein 141, Glycine Phosphate, GPIbA, CD44 antigen, Monosodium Salt Glycine, Malignant Melanomas, Copper Salt Glycine, multicellular organismal lipid catabolic process, DmIKKgamma, DmelCG7664, Benign, symptom cluster, Marker, ly-24, dIKK, DAMAGE, Hepatocellular carcinoma-associated protein 1, shelf, GPIba, simple tissue, DNA Oxidative Damages, Acid, HUTCH-I, End Points, Glycine Sulfate (3:1), Glycerophospholipids, IKK-gamma, Benign Neoplasms, Immunologic, Cobalt Salt, 2-amino-3-carbamoylpropanoic acid, Laboratory Marker, projection, ridge, GPIb-alpha, Malignant Neoplasms, Nitro-Oxidative, polyunsaturated phosphatidylcholine, Muscular atrophy, Platelet, DNA, EPA, PTPbeta2, platelet, other neoplasm, GP1B, Aa1249, Oxidative Damage, CD42b-alpha, lipids, TIMP-1, EPO, Cysteine-rich protein 1, DBPLT3, Peptidomics, lamellae, Antioxidative, Clinical Marker, Neoplasms, developmental stage, 35F(AT)[[17]], Hasp, Serum Protein, AI450271, biosynthesis, syndromic disease or disorder, process of organ, dIKK-gamma, lamella, melanoma (disease), IN, CYRP, urinary form, DmIKK-gamma, 4732461B14Rik, symptom clusters, Gene Products, Phosphatidyl, Oxidative Damages, portion of blood, Injury, Clinical, CO4, Naevocarcinoma, Monosodium Salt, syndrome, AI847422, syndromes, Ac1-114, Symptom, CPAMD2, synthesis, Neoplasias, Plasma Protein, l(2)k03505, Phagocytic glycoprotein I, CSPG8, anatomical unit, Antioxidative Stresses, 0610010I23Rik, body organ, bodyfat, AI255847, GPIbalpha, laminae, Thrombocyte, Biologic, Cancer, Malignant Neoplasm, 3-sn-Phosphatidylcholine, whole blood, Phagocytic glycoprotein 1, Monopotassium Salt Glycine, Serum Markers, Proteins, Copper Salt, Phosphatidyl Cholines, Phosphoglycerides, NG2, qkr, Anti-oxidative Stresses, l(3)S090417, Amyotrophy involving the extremities, Immune Marker, IKKgamma, AN2, MT, C4-1, Surrogate End Point, Symptom Cluster, Icosanoid, amyotrophia, Oxidative Nitrative Stresses, Malignant Melanoma, KH93F, chemical analysis, Neoplasm, Cholines, CD148, HCELL, organ process, Biologic Markers, Crp, CRP, primary cancer, Muscle wasting, Anti-oxidative Stress, Neurogenic muscular atrophy, DNA Oxidative Damage, RGD1560259, Surrogate, MS:35F.AT17, Dmikkgamma, extracellular matrix receptor III, Endpoints, bHLHe63, postnatal growth, Monopotassium Salt, Cancers, HMW-MAA, cytoplasmic release of stored calcium ion (Ca2+), Glyzin, enucleate thrombocyte, CG16910, 4-diamino-4-oxobutanoic acid, malignant tumor, Phosphatidyl Choline, Gene Proteins, processes, AP4, dAP-4, adipose, Ac2-069, Aminoacetic, Glykokoll, Stress, DBMT1, PC, Neoplasia, Calcium Salt, C77570, GP-Ib alpha, GP90 lymphocyte homing/adhesion receptor, Immune Markers, cluster, DNA Oxidative, Ly-24, Glycine Carbonate (2:1), Biological Markers, Viral Marker, HDLCQ9, AU023126, AP-4, Calcium Salt Glycine, determination, H2N-CH2-COOH, Epican, DEP-1, Feature, Blood, CD44A, postnatal development, Biochemical, Metabonomic, Endpoint, Nitrative Stress, Phosphatidyl-N-trimethylethanolamine, CG7664, neutral molecular compounds, Monoammonium, Serum, Monosodium, Damage, element, BSS, C4S, Laboratory Markers, especially in the lower limbs, Thrombocytes, melanoma, Calcium Salt (2:1), Lymphocyte antigen 24, Nitro-Oxidative Stress, C4b, Monoammonium Salt Glycine, symptom, multicellular organism lipid catabolic process, gp300, RG, Oxidative Injury, fatty tissue, molecule, IKKg, l(3)j5D5, fat tissue, DEP1, Pgp1, KEY, Key, multicellular organismal biosynthetic process, molecula, 24B, single-organism biosynthetic process, Lecithin, Oxidative Injuries, antigen CD42b-alpha, adipose system, CD42B, AW743261, Phosphate, release of sequestered calcium ion into cytoplasm, MCSP, LHR, Oxidative DNA Damages, Estimated, CD14, CG10293, heparan sulfate proteoglycan, ASN, Asn, Anti-oxidative, l(3)j5B5, Oxidative Stress Injuries, Immune, Markers, anucleate thrombocyte, malignant neoplasm, HCA1, syndromic disease, Viral Markers, CD42b, papilla, muscle wasting, MDU2, MDU3, Malignancies, METAA, 0904/17, Surrogate Endpoint, PLATEST, Icosanoids, CRP4, CRP2, CRP1, lamina, Blood Platelet, MC56, flanges, Neurogenic muscle atrophy, Biochemical Markers, Clusters, aminoethanoic acid, Biologic Marker, hermes antigen, Multiple Reaction Monitoring, GP90 lymphocyte homing|adhesion receptor, AW146109, Hermes antigen, Body Fat, Melanoma, GP1BA, SZ1, Oxidative and Nitrosative Stress, neurogenic, Wasting syndrome, Lipid, HCI, Kenny, CSRP, crp.4a, internal to cell, SCC1, Scc1, CD44, Ab1-341, CDW44, l(2)00232, MIC4, growth pattern, non-developmental growth, Hgly, shelves, Byp, Features, clusters, Timp, Muscle atrophy, Crpd, metastatic, CDw44, DmelCG16910, Syndromes, Cluster, Patient, Biochemical Marker, ECMR-III, blood platelet, anon-EST:Liang-2.39, Oxidative Stress Injury, RPTPJ, Wasting syndrome., mMage-e1, Platelets, TIMP, AW121933, Ba2-693, CIB8, Oxidative Stress, CRP-[a], Sodium Hydrogen Carbonate, Clinical Markers, Clgi, Lecithol, P62, RHAMM, Monopotassium, Benign Neoplasm, Antioxidative Stress, Gene, CLGI, l(2)35Fd, fat, Malignant, Monocyte differentiation antigen CD14, Surrogate End Points, Stresses, Lipolyses, Surrogate Markers, VWDP, l(2)SH1614, Oxidative Nitrative, Stress Injury, ESP1, thrombocyte, l(2)k00809, Oxidative Cleavages, Glycine Hydrochloride (2:1), dmIKKgamma, Metabolomic, IKK[[gamma]], Choline Glycerophospholipids, protoplasm, Ptpb2, Biomarker, calcium mobilization, epican, Glycine Hydrochloride, l(3)s2612, MRM, protoplast, Malignancy, formation, Biological Marker, phagocytic glycoprotein I, Serum Proteins, ridges, Plasma Proteins, Asparagin, release of stored calcium ion (Ca2+), Immunologic Markers, Muscle degeneration, CRP-[b], Salt Glycine, Glycin, phagocytic glycoprotein 1, IKK, Anti oxidative Stress, p80, phosphatidylcholines, Oxidative DNA Damage, Clients, DmelCG10293, Phospholutein, Leimzucker, 2-aminoacetic acid, Characteristics, Choline, Immunologic Marker, BG:DS02740.3, Monoammonium Salt, calcium ion (Ca2+) mobilization, Glycine Phosphate (1:1), HPTPeta, ptx1, clone 2.39, malignant, vertebrate blood, Alpha-dystrobrevin-associated MAGE Protein, Aminoacetic acid, End Point, Eicosanoid, Client, Heparan sulfate proteoglycan, development, Melanomas, Oxidative Nitrative Stress, Glycine Carbonate (1:1), Characteristic, Ac1262, Myeloid cell-specific leucine-rich glycoprotein, Protein, Hydrochloride, membrane-bound form, flange, 2-Diacyl-sn-glycero-3-phosphocholine, who, Plasma, Aminoacetic Acid, Serum Marker, Hlp, glycoprotein Ibalpha, l(2)SH2 1614, Ab2-196, Who/How, Monolithium Salt, release of sequestered calcium ion (Ca2+), Cleavage, Choline Phosphoglycerides, Surrogate Marker, Protein Gene Products, lymphocyte antigen 24, fatty depot, qkr[93F], MEL-CSPG, malignant melanoma, assay, PTX1, Nitro Oxidative Stress, growthPanomics, organ, Multi Omics, calcium ion (Ca2+) mobilization, calcium mobilization, Integrative-Omics, determination, Activation, malignant, Blood, platelet activation, Integrative, release of sequestered calcium ion into cytoplasm, Omics, Malignant Melanomas, cytoplasmic release of stored calcium ion (Ca2+), Blood Serum, Serum, release of sequestered calcium ion (Ca2+), Naevocarcinoma., Integrative Omics, Malignant, element, Multi-Omics, release of stored calcium ion (Ca2+), melanoma (disease), metastatic, Melanomas, blood coagulation, Melanoma, melanoma, anatomical unit, Malignant Melanoma, chemical analysis, body organ, Multi-Omic, Pan Omics, Platelet, Activations, Pan-Omics, malignant melanoma, release of stored calcium ion (Ca2+) into cytoplasm, assay, Platelet Activations, cytoplasmic release of sequestered calcium ion (Ca2+), Serumscalcium ion (Ca2+) mobilization, Malignant Neoplasm, determination, malignant, Blood, Neoplasms, Proteins, Benign Neoplasm, Gene, Malignant Melanomas, Blood Serum, Serum, Tumor, Malignant, Client, element, melanoma (disease), Melanomas, Melanoma, Benign, melanoma, Malignant Melanoma, chemical analysis, Protein, Gene Products, Neoplasm, Platelet Activations, metastatic melanoma, organ, calcium mobilization, Activation, Malignancy, platelet activation, Naevocarcinoma, Benign Neoplasms, release of sequestered calcium ion into cytoplasm, Cancers, cytoplasmic release of stored calcium ion (Ca2+), release of sequestered calcium ion (Ca2+), Protein Gene Products, release of stored calcium ion (Ca2+), Neoplasias, Gene Proteins, blood coagulation, Patient, anatomical unit, Clients, body organ, Platelet, Activations, malignant melanoma, release of stored calcium ion (Ca2+) into cytoplasm, Malignancies, assay, cytoplasmic release of sequestered calcium ion (Ca2+), other neoplasm, metastatic malignant melanoma, Serums, Neoplasia, Cancer, Tumors, Malignant Neoplasms.0PXD004624trueMulti-omics analysis of serum samples demonstrates reprogramming of organ functions via systemic calcium mobilization and platelet activation in metastatic melanoma patients – proteins from serum samples of melanoma patients with high tumor loadPathophysiology of cancer-associated syndroms such as cachexia is poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting on nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44 and CO4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics. Remarkably, these molecules are known to be involved in key processes of cancer cachexia. Based on these results, we propose a model how metastatic melanoma may lead to reprogramming of organ functions via formation of platelet activating factors from long-chain polyunsaturated phosphatidylcholines under oxidative conditions and via systemic induction of intracellular calcium mobilization. Calcium mobilization in platelets was demonstrated to regulate several of these marker molecules. Additionally, platelets from melanoma patients proved to be in a rather exhausted state, and platelet-derived eicosanoids implicated in tumor growth were found massively increased in blood from three melanoma patients. Platelets were thus identified as important source of serum protein and lipid alterations in late stage melanoma patients. As a result, the proposed model describes the crosstalk between lipolysis of fat tissue and muscle wasting mediated by oxidative stress, resulting in the metabolic deregulations characteristic for cachexia.Thu Jan 31 13:32:00 GMT 2019MSV00008338527879288