Serum Amyloid A As a Prognostic Marker in Melanoma Identified by Proteomic Profiling

被引:89
作者
Findeisen, Peter
Zapatka, Marc
Peccerella, Teresa
Matzk, Heike
Neumaier, Michael
Schadendorf, Dirk
Ugurel, Selma
机构
[1] Univ Heidelberg, Inst Clin Chem, Med Fac Mannheim, D-6900 Heidelberg, Germany
[2] German Canc Res Ctr, Dept Theoret Bioinformat, Heidelberg, Germany
[3] German Canc Res Ctr, Skin Canc Unit, Heidelberg, Germany
[4] Univ Hosp Mannheim, Dept Dermatol, Mannheim, Germany
关键词
LASER-DESORPTION/IONIZATION-TIME; AMERICAN JOINT COMMITTEE; C-REACTIVE PROTEIN; FLIGHT MASS-SPECTROMETRY; LUNG-CANCER; PLASMA PROTEOME; OVARIAN-CANCER; DISEASE; BIOMARKERS; STAGE;
D O I
10.1200/JCO.2008.18.0554
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Purpose Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Patients and Methods Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. Results MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. Conclusion SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.
引用
收藏
页码:2199 / 2208
页数:10
相关论文
共 26 条
[1]
The human plasma proteome - History, character, and diagnostic prospects [J].
Anderson, NL ;
Anderson, NG .
MOLECULAR & CELLULAR PROTEOMICS, 2002, 1 (11) :845-867
[2]
Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system [J].
Balch, CM ;
Soong, SJ ;
Gershenwald, JE ;
Thompson, JF ;
Reintgen, DS ;
Cascinelli, N ;
Urist, M ;
McMasters, KM ;
Ross, MI ;
Kirkwood, JM ;
Atkins, MB ;
Thompson, JA ;
Coit, DG ;
Byrd, D ;
Desmond, R ;
Zhang, YT ;
Liu, PY ;
Lyman, GH ;
Morabito, A .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3622-3634
[3]
Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma [J].
Balch, CM ;
Buzaid, AC ;
Soong, SJ ;
Atkins, MB ;
Cascinelli, N ;
Coit, DG ;
Fleming, ID ;
Gershenwald, JE ;
Houghton, A ;
Kirkwood, JM ;
McMasters, KM ;
Mihm, MF ;
Morton, DL ;
Reintgen, DS ;
Ross, MI ;
Sober, A ;
Thompson, JA ;
Thompson, JF .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3635-3648
[4]
Standardized approach to proteome profiling of human serum based on magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry [J].
Baumann, S ;
Ceglarek, U ;
Fiedler, GM ;
Lembcke, J ;
Leichtle, A ;
Thiery, J .
CLINICAL CHEMISTRY, 2005, 51 (06) :973-980
[5]
SERUM AMYLOID-A (SAA) VARIATIONS IN PATIENTS WITH CANCER - CORRELATION WITH DISEASE-ACTIVITY, STAGE, PRIMARY SITE, AND PROGNOSIS [J].
BIRAN, H ;
FRIEDMAN, N ;
NEUMANN, L ;
PRAS, M ;
SHAINKINKESTENBAUM, R .
JOURNAL OF CLINICAL PATHOLOGY, 1986, 39 (07) :794-797
[6]
Deichmann M, 2000, J EXP CLIN CANC RES, V19, P301
[7]
Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase [J].
Deichmann, M ;
Kahle, B ;
Moser, K ;
Wacker, J ;
Wüst, K .
BRITISH JOURNAL OF CANCER, 2004, 91 (04) :699-702
[8]
Protein arrays - Growing pains [J].
Eisenstein, Michael .
NATURE, 2006, 444 (7121) :959-964
[9]
Preanalytical impact of sample handling on proteome profiling experiments with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry [J].
Findeisen, P ;
Sismanidis, D ;
Riedl, M ;
Costina, V ;
Neumaier, M .
CLINICAL CHEMISTRY, 2005, 51 (12) :2409-2411
[10]
Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis [J].
Gao, WM ;
Kuick, R ;
Orchekowski, RP ;
Misek, DE ;
Qiu, J ;
Greenberg, AK ;
Rom, WN ;
Brenner, DE ;
Omenn, GS ;
Haab, BB ;
Hanash, SM .
BMC CANCER, 2005, 5 (1)