Protein signatures for survival and recurrence in metastatic melanoma.

Patients with melanoma metastatic to regional lymph nodes exhibit a range in tumor progression, survival, and treatment. Current approaches to stratify patients with this stage of disease predominantly involve clinical and histological methods. Molecular classification thus far has focused almost exclusively on genetic mutations. In this study, proteomic data from 69 melanoma lymph node metastases and 17 disease free lymph nodes acquired by histology-directed MALDI imaging mass spectrometry were used to classify tumor from control lymph node and to molecularly sub-classify patients with stage III disease. From these data, 12 survival associated protein signals and 3 recurrence associated signals in the acquired mass spectra were combined to generate a multiplex molecular signature to group patients into either poor or favorable groups for recurrence and survival. Proteins represented in the signature include cytochrome c, s100 A6, histone H4, and cleaved forms of thymosin β-4, thymosin β-10, and ubiquitin. In total over 40 protein signals from the tissue were identified.

[1]  Baogang J. Xu,et al.  MALDI‐MS derived prognostic protein markers for resected non‐small cell lung cancer , 2008, Proteomics. Clinical applications.

[2]  J. Zubovits,et al.  HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. , 2004, Human pathology.

[3]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M. Ringnér,et al.  Gene Expression Profiling–Based Identification of Molecular Subtypes in Stage IV Melanomas with Different Clinical Outcome , 2010, Clinical Cancer Research.

[5]  G. Zummo,et al.  Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics , 2006, Cancer biology & therapy.

[6]  K. Schey,et al.  MALDI tissue profiling of integral membrane proteins from ocular tissues , 2008, Journal of the American Society for Mass Spectrometry.

[7]  Richard M Caprioli,et al.  A Novel Histology-directed Strategy for MALDI-MS Tissue Profiling That Improves Throughput and Cellular Specificity in Human Breast Cancer* , 2006, Molecular & Cellular Proteomics.

[8]  K. Schey,et al.  Optimization of a MALDI TOF-TOF mass spectrometer for intact protein analysis , 2005, Journal of the American Society for Mass Spectrometry.

[9]  R. Weinberg,et al.  A molecular basis of cancer. , 1983, Scientific American.

[10]  J C Briggs,et al.  Cutaneous melanoma. , 1993, Journal of the American Academy of Dermatology.

[11]  D. Schadendorf,et al.  Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Richard M Caprioli,et al.  Early Changes in Protein Expression Detected by Mass Spectrometry Predict Tumor Response to Molecular Therapeutics , 2004, Cancer Research.

[13]  Y. Samuels,et al.  Analysis of the genome to personalize therapy for melanoma , 2010, Oncogene.

[14]  M. Birrer,et al.  Thymosin B 4 Is a Determinant of the Transformed Phenotype and Invasiveness of S-Adenosylmethionine Decarboxylase – Transfected Fibroblasts , 2006 .

[15]  Baogang J. Xu,et al.  Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry , 2003, Proteomics.

[16]  Eric S. Lander,et al.  Genomic analysis of metastasis reveals an essential role for RhoC , 2000, Nature.

[17]  Tak W. Mak,et al.  Cytochrome c: functions beyond respiration , 2008, Nature Reviews Molecular Cell Biology.

[18]  A. Filipek,et al.  S100A6 - new facts and features. , 2009, Biochemical and biophysical research communications.

[19]  M. Grunstein Histone acetylation in chromatin structure and transcription , 1997, Nature.

[20]  Elias S. J. Arnér,et al.  Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. , 2001, Free radical biology & medicine.

[21]  C. Garbe,et al.  Diagnosis and treatment of cutaneous melanoma: state of the art 2006. , 2007, Melanoma research.

[22]  Yu Shyr,et al.  Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. , 2005, Cancer research.

[23]  Richard M Caprioli,et al.  Imaging mass spectrometry reveals unique protein profiles during embryo implantation. , 2008, Endocrinology.

[24]  B. Zetter,et al.  C‐terminal variations in β‐thymosin family members specify functional differences in actin‐binding properties , 2000, Journal of cellular biochemistry.

[25]  V. Hearing,et al.  The Regulation of Skin Pigmentation* , 2007, Journal of Biological Chemistry.

[26]  L. Fecher,et al.  Toward a molecular classification of melanoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  Michelle L. Reyzer,et al.  Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. , 2003, Journal of mass spectrometry : JMS.

[28]  R. Kay The Analysis of Survival Data , 2012 .

[29]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.

[30]  D. Ruiter,et al.  Thymosin β‐10 expression in melanoma cell lines and melanocytic lesions: A new progression marker for human cutaneous melanoma , 1993, International journal of cancer.

[31]  Richard M. Caprioli,et al.  Solvent-free matrix dry-coating for MALDI imaging of phospholipids , 2008, Journal of the American Society for Mass Spectrometry.

[32]  P. Selby,et al.  Identification of proteins regulated by interferon‐α in resistant and sensitive malignant melanoma cell lines , 2004, Proteomics.

[33]  M. Quadroni,et al.  Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stage , 2008, Proteomics.

[34]  P. Chaurand,et al.  Processing MALDI Mass Spectra to Improve Mass Spectral Direct Tissue Analysis. , 2007, International journal of mass spectrometry.

[35]  Walter A. Korfmacher,et al.  Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry. , 2003, Journal of mass spectrometry : JMS.

[36]  S. Liao,et al.  Differential thymosin beta 10 expression levels and actin filament organization in tumor cell lines with different metastatic potential. , 2004, Chinese medical journal.

[37]  John David,et al.  Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: Regulatory role in the innate immune response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Eggermont,et al.  Gene expression profiling of primary cutaneous melanoma and clinical outcome. , 2006, Journal of the National Cancer Institute.

[39]  Richard M Caprioli,et al.  Molecular analysis of tumor margins by MALDI mass spectrometry in renal carcinoma. , 2010, Journal of proteome research.

[40]  R. Caprioli,et al.  Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. , 2006, Analytical chemistry.

[41]  R. Caprioli,et al.  Direct profiling of the cerebellum by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry: A methodological study in postnatal and adult mouse , 2005, Journal of neuroscience research.

[42]  Richard M Caprioli,et al.  Molecular profiling of experimental Parkinson's disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. , 2004, Journal of proteome research.

[43]  R. Caprioli Deciphering protein molecular signatures in cancer tissues to aid in diagnosis, prognosis, and therapy. , 2005, Cancer research.

[44]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[45]  O. Podhajcer,et al.  Proteomic analysis identified N‐cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells , 2007, Proteomics.

[46]  R. Marais,et al.  Melanoma biology and new targeted therapy , 2007, Nature.

[47]  K. Schey,et al.  Fragmentation of multiply-charged intact protein ions using MALDI TOF-TOF mass spectrometry , 2008, Journal of the American Society for Mass Spectrometry.

[48]  D. Morton,et al.  Detection of Differentially Expressed Proteins in Early‐Stage Melanoma Patients Using SELDI‐TOF Mass Spectrometry , 2004, Annals of the New York Academy of Sciences.

[49]  M. Herlyn,et al.  A systems biology analysis of metastatic melanoma using in‐depth three‐dimensional protein profiling , 2010, Proteomics.

[50]  G. Salvesen,et al.  The apoptosome: signalling platform of cell death , 2007, Nature Reviews Molecular Cell Biology.

[51]  R. Donato,et al.  Intracellular and extracellular roles of S100 proteins , 2003, Microscopy research and technique.

[52]  T. Mohr,et al.  Entering a new era of rational biomarker discovery for early detection of melanoma metastases: secretome analysis of associated stroma cells. , 2009, Journal of proteome research.

[53]  H. Yin,et al.  The β‐Thymosin Enigma , 2007 .

[54]  Walter A. Korfmacher,et al.  Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue. , 2006, Rapid communications in mass spectrometry : RCM.

[55]  Baogang J. Xu,et al.  Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. , 2008, Journal of proteome research.

[56]  M. Stoeckli,et al.  Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections , 2007 .

[57]  Richard M Caprioli,et al.  New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. , 2006, Journal of proteome research.

[58]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[59]  R. Caprioli,et al.  Tissue profiling MALDI mass spectrometry reveals prominent calcium‐binding proteins in the proteome of regenerative MRL mouse wounds , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[60]  Barbara A Pockaj,et al.  Malignant melanoma in the 21st century, part 2: staging, prognosis, and treatment. , 2007, Mayo Clinic proceedings.

[61]  U. G. Dailey Cancer,Facts and Figures about. , 2022, Journal of the National Medical Association.

[62]  Danton H O'Day,et al.  CaMBOT: profiling and characterizing calmodulin-binding proteins. , 2003, Cellular signalling.

[63]  D. Tobin,et al.  Melanin pigmentation in mammalian skin and its hormonal regulation. , 2004, Physiological reviews.

[64]  F. Greene,et al.  AJCC cancer staging handbook : from the AJCC cancer staging manual , 2002 .

[65]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[66]  R. Caprioli,et al.  Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. , 2007, Journal of mass spectrometry : JMS.

[67]  I. Rennie,et al.  Attachment of human uveal melanocytes and melanoma cells to extracellular matrix proteins involves intracellular calcium and calmodulin , 1997, Melanoma research.

[68]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[69]  H. Yin,et al.  The beta-thymosin enigma. , 2007, Annals of the New York Academy of Sciences.

[70]  D. Ruiter,et al.  Expression of calcyclin in human melanocytic lesions. , 1993, Cancer research.

[71]  Bill C. White,et al.  Proteomic patterns of tumour subsets in non-small-cell lung cancer , 2003, The Lancet.

[72]  A. Anichini,et al.  APAF-1 signaling in human melanoma. , 2006, Cancer letters.

[73]  N. Sampas,et al.  Molecular classification of cutaneous malignant melanoma by gene expression profiling , 2000, Nature.