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. 2010 Jan;130(1):221-9.
doi: 10.1038/jid.2009.195.

Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma

Yasufumi Goto  1 , Kazuo Koyanagi, Norihiko Narita, Yutaka Kawakami, Minoru Takata, Aya Uchiyama, Linhda Nguyen, Tung Nguyen, Xing Ye, Donald L Morton, Dave S B Hoon
Affiliations

Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma

Yasufumi Goto et al. J Invest Dermatol. 2010 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1. Receiver operating characteristic of FABP7 in primary melanoma
The AUC of FABP7 is 0.824 (P<0.0001).
Figure 2
Figure 2. Ratio of the FABP7/GAPDH mRNA copies in melanoma lines and tissues
The cutoff point (dotted line) for FABP7 positivity was set at 0.0011 (the mean ratio of the FABP7/GAPDH mRNA copies plus 3 SD of normal human skin controls). Horizontal bars denote mean mRNA copies and SEM.
Figure 3
Figure 3. FABP7 mRNA expression in metastatic tumors related to disease outcome
Kaplan–Meier estimates of relapse-free survival (a) and overall survival (b) based on FABP7 mRNA detection in melanoma metastases.
Figure 4
Figure 4. Location of FABP7 gene and the three microsatellite markers used for LOH assessment on chromosome 6
FABP7 gene is located at 6q22.31, between D6S268 and D6S1702.
Figure 5
Figure 5. FABP7 mRNA expression, LOH status, IHC analysis of melanoma cell lines with polyclonal rabbit anti-FABP7 Ab
Small bars represent SD. LOH, loss of heterozygosity; R, retention of alleles; +, IHC stained; −, IHC shows not stained; N/A, not available for analysis.
Figure 6
Figure 6. Melanoma cell spiking of PBLs
FABP7 qRT quantification of serially diluted melanoma cells (103 102, 101, 10, and 0 cells) mixed with 107 normal PBLs. A mean of absolute mRNA copy numbers are given. Small bars represent SD. This is a representative of three assays.
Figure 7
Figure 7. FABP7/GAPDH mRNA copy ratios in blood from healthy donors and melanoma patients
Horizontal bars denote mean mRNA copies. P<0.0001.
See this image and copyright information in PMC

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