LC/MS-based quantitative proteomic analysis of paraffin-embedded archival melanomas reveals potential proteomic biomarkers associated with metastasis.
BACKGROUND
Melanoma metastasis status is highly associated with the overall survival of patients; yet, little is known about proteomic changes during melanoma tumor progression. To better understand the changes in protein expression involved in melanoma progression and metastasis, and to identify potential biomarkers, we conducted a global quantitative proteomic analysis on archival metastatic and primary melanomas.


RESULTS
A total of 16 metastatic and 8 primary cutaneous melanomas were assessed. Proteins were extracted from laser captured microdissected formalin fixed paraffin-embedded archival tissues by liquefying tissue cells. These preparations were analyzed by a LC/MS-based label-free protein quantification method. More than 1500 proteins were identified in the tissue lysates with a peptide ID confidence level of >75%. This approach identified 120 significant changes in protein levels. These proteins were identified from multiple peptides with high confidence identification and were expressed at significantly different levels in metastases as compared with primary melanomas (q-Value<0.05).


CONCLUSIONS
The differentially expressed proteins were classified by biological process or mapped into biological system networks, and several proteins were implicated by these analyses as cancer- or metastasis-related. These proteins represent potential biomarkers for tumor progression. The study successfully identified proteins that are differentially expressed in formalin fixed paraffin-embedded specimens of metastatic and primary melanoma.
Huang
Sharon K
SK
Department of Molecular Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, United States of America.
Darfler
Marlene M
MM
Nicholl
Michael B
MB
You
Jinsam
J
Bemis
Kerry G
KG
Tegeler
Tony J
TJ
Wang
Mu
M
Wery
Jean-Pierre
JP
Chong
Kelly K
KK
Nguyen
Linhda
L
Scolyer
Richard A
RA
Hoon
Dave S B
DS
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods; D030562:Databases, Protein; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008545:Melanoma / Q000737:chemistry / Q000473:pathology; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D016612:Paraffin Embedding; D020543:Proteome / Q000032:analysis*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome