title: Clinical utility of serum autoantibodies detected by protein microarray in melanoma.
abstract: Better prognostic and predictive markers in melanoma are needed to select patients for therapy. We utilized a dual-lectin affinity chromatography and a natural protein microarray-based analysis to select a subproteome of target glycoproteins to profile serum antibodies against melanoma associated antigens that may predict nodal positivity. We identified 5 melanoma-associated antigens using this microarray coupled to mass spectrometry; GRP75, GRP94, ASAH1, CTSD and LDHB. We evaluated their predictive value for nodal status adjusting for age, gender, Breslow thickness, mitotic rate and ulceration using standard logistic regression. After adjustment, ASAH1, CTSD and LDHB were significantly negatively associated with nodal status (P = 0.0008) and GRP94 was significantly positively associated (P = 0.014). Our best multivariate model for nodal positivity included Breslow thickness, presence of serum anti-ASAH1, anti-LDHB or anti-CTSD, and presence of serum anti-GRP94, with an area under the ROC curve of 0.869. If validated, these results show promise for selecting clinically node negative patients for SLN biopsy. In addition, there is strong potential for glycoprotein microarray to screen serum autoantibodies that may identify patients at high risk of distant metastases or those likely or unlikely to respond to treatment, and these proteins may serve as targets for intervention.
authors.affiliation: Department of Surgery, University of Michigan Health Systems Biostatistics Core, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabel
authors.forename: Yashu
authors.initials: Y
authors.lastname: Liu
authors.forename: Kent A
authors.initials: KA
authors.lastname: Griffith
authors.forename: Jintang
authors.initials: J
authors.lastname: He
authors.forename: Xaiolei
authors.initials: X
authors.lastname: Xie
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
references.citation: J Invest Dermatol. 1995 Mar;104(3):340-4
references.pmid: 7860998
references.citation: Coll Antropol. 2007 Jan;31 Suppl 1:7-11
references.pmid: 17469741
references.citation: Curr Drug Targets. 2008 Aug;9(8):653-61
references.pmid: 18691012
references.citation: Oncogene. 2003 May 19;22(20):3180-7
references.pmid: 12789294
references.citation: Adv Immunol. 2006;90:215-41
references.pmid: 16730265
references.citation: Anticancer Res. 1998 Sep-Oct;18(5B):3785-8
references.pmid: 9854496
references.citation: Mol Ther. 2009 Mar;17(3):430-8
references.pmid: 19107118
references.citation: Arch Dermatol. 2004 Jan;140(1):107-13
references.pmid: 14732667
references.citation: Science. 2001 Mar 23;291(5512):2370-6
references.pmid: 11269318
references.citation: J Clin Oncol. 2009 Dec 20;27(36):6199-206
references.pmid: 19917835
references.citation: Eur J Cancer. 2002 Jul;38(11):1501-11
references.pmid: 12110497
references.citation: J Proteome Res. 2010 Nov 5;9(11):6044-51
references.pmid: 20879797
references.citation: Expert Rev Mol Diagn. 2010 Oct;10(7):897-919
references.pmid: 20964610
references.citation: Expert Opin Ther Targets. 2009 Dec;13(12):1449-58
references.pmid: 19874262
references.citation: Clin Exp Metastasis. 2004;21(2):91-106
references.pmid: 15168727
references.citation: J Am Coll Surg. 1995 Sep;181(3):193-201
references.pmid: 7670677
references.citation: J Clin Invest. 2002 Jul;110(1):3-8
references.pmid: 12093880
references.citation: Oncology. 1999 Apr;56(3):208-14
references.pmid: 10202276
references.citation: Int J Cancer. 1999 May 31;81(5):700-4
references.pmid: 10328219
references.citation: APMIS. 1999 Jan;107(1):86-95
references.pmid: 10190284
references.citation: Climacteric. 2009 Dec;12(6):502-13
references.pmid: 19905902
references.citation: J Clin Oncol. 2000 Nov 15;18(22):3782-93
references.pmid: 11078491
references.citation: Ann Oncol. 2008 Mar;19(3):590-4
references.pmid: 18037622
references.citation: Pathol Res Pract. 1999;195(3):171-5
references.pmid: 10220797
references.citation: Melanoma Res. 2009 Feb;19(1):31-5
references.pmid: 19104452
references.citation: Int J Dermatol. 2000 Aug;39(8):599-602
references.pmid: 10971728
references.citation: Curr Opin Immunol. 1998 Feb;10(1):93-102
references.pmid: 9523118
references.citation: Pigment Cell Res. 2003 Jun;16(3):254-60
references.pmid: 12753398
references.citation: J Exp Med. 1994 Aug 1;180(2):525-35
references.pmid: 8046331
references.citation: Arch Dermatol Res. 1995;287(3-4):266-72
references.pmid: 7598531
references.citation: Curr Pharm Des. 2006;12(35):4625-35
references.pmid: 17168766
references.citation: Cancer Res. 1997 Apr 1;57(7):1270-5
references.pmid: 9102212
references.citation: J Mol Biol. 1999 Oct 22;293(2):351-66
references.pmid: 10529350
references.citation: Cancer. 2001 Mar 1;91(5):972-82
references.pmid: 11251949
references.citation: Cancer Invest. 2008 Jul;26(6):624-33
references.pmid: 18584354