Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma.
Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma.
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DOI：
10.1038/jid.2009.195
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发表时间：
2010-01
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脂肪酸结合蛋白-7(FABP7)已被证明在皮肤黑色素瘤中表达，但其在肿瘤进展中的作用尚不清楚。通过评估原发肿瘤进展和转移的不同临床病理阶段，评估FABP7在黑色素瘤进展过程中的表达。FABP7mRNA在87例原发黑色素瘤中有60例(69%)高表达，而在68例转移性黑色素瘤中有13例(19%)显著降低(P<；0.0001)。免疫组织化学检测37例原发黑色素瘤和转移性黑色素瘤，阳性率分别为73%和27%(P<；0.001)。转移组织中FABP7的检测与无复发(P<；0.0001)和总生存率(P<；0.0001)呈负相关。为了检测进展期黑色素瘤中FABP7的表达缺失，使用包含FABP7基因的微卫星标记评估了杂合性缺失(LOH)。转移性黑色素瘤中有10例(50%)在6q22.31有杂合性缺失，而在14例原发黑色素瘤中则为0(P=0.0017)。采用实时定量聚合酶链式反应(QRT-PCR)对134例黑色素瘤患者血液中FABP7作为循环肿瘤细胞(CTCs)的替代标志物进行了研究。对患者血液的评估显示，FABP7(+)CTC随着疾病的进展而降低。FABP7可能作为肿瘤进展基因发挥作用，可作为早期黑色素瘤全身性血液播散的潜在诊断标志物。
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.