Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma.
Fatty acid-binding protein-7 (FABP7) has been shown to be expressed in cutaneous melanoma; however, its role in tumor progression is unclear. Expression of FABP7 was assessed during melanoma progression through assessment of various clinicopathology stages of primary tumor progression and metastasis. FABP7 mRNA was highly expressed in 60 of 87 (69%) primary melanomas, compared with significant (P<0.0001) reduction in 13 of 68 (19%) metastatic melanomas. Analysis of 37 paired primary and metastatic melanomas by immunohistochemistry with anti-FABP7 Ab showed 73 and 27% positivity, respectively (P<0.001). FABP7 detection of metastatic tissues was inversely correlated with relapse-free (P<0.0001) and overall (P<0.0001) survival. To examine FABP7 expression loss in advanced melanomas, loss of heterozygosity (LOH) was assessed using microsatellite markers encompassing the FABP7 gene. LOH was identified in 10 of 20 (50%) metastatic melanomas at 6q22.31, compared with 0 of 14 primary melanomas (P=0.0017). FABP7 as a surrogate biomarker for circulating tumor cells (CTCs) in the blood was assessed by quantitative real-time (qRT)-PCR from melanoma patients' blood (n=134). Assessment of patients' blood showed that FABP7(+) CTC decreased with disease progression. FABP7 may function as a tumor progression gene and can be used as a potential diagnostic biomarker of early-stage melanoma systemic spreading in blood.
Goto
Yasufumi
Y
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California, USA.
Koyanagi
Kazuo
K
Narita
Norihiko
N
Kawakami
Yutaka
Y
Takata
Minoru
M
Uchiyama
Aya
A
Nguyen
Linhda
L
Nguyen
Tung
T
Ye
Xing
X
Morton
Donald L
DL
Hoon
Dave S B
DS
D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6; D018450:Disease Progression; D018572:Disease-Free Survival; D000071438:Fatty Acid-Binding Protein 7; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D009360:Neoplastic Cells, Circulating; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins