Identification of glypican-3 as a novel tumor marker for melanoma
Identification of glypican-3 as a novel tumor marker for melanoma
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DOI：
10.1158/1078-0432.ccr-04-0348
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发表时间：
2004-10-01
影响因子：
11.5
通讯作者：
Nishimura, Y
中科院分区：
文献类型：
--
作者：
Nakatsura, T;Kageshita, T;Nishimura, Y
目的：我们最近报道了用于肝细胞癌的新型肿瘤标志物磷脂酰肌醇蛋白聚糖-3 (GPC3)。在本研究中，我们研究了GPC3在人黑色素瘤细胞系和组织中的表达，并探讨GPC3是否可以成为黑色素瘤的新型肿瘤标志物。实验设计：使用逆转录PCR和免疫组织化学分析研究了GPC3 mRNA和蛋白在人黑色素瘤细胞系和组织中的表达。使用 ELISA 对黑色素瘤细胞系培养上清液以及 91 名黑色素瘤患者和 28 名原发性黑色素瘤手术切除后无病患者的血清中分泌的 GPC3 蛋白进行定量。所有受试者均为日本国民。结果：在>80%的黑色素瘤和黑素细胞痣中，有明显的GPC3 mRNA和蛋白表达。此外，39.6%（91 名中的 36 名）黑色素瘤患者的血清中发现了 GPC3 蛋白，但在患有大面积先天性黑素细胞痣的受试者（5 名中的 0 名）和健康捐献者（60 名中的 0 名）的血清中没有发现 GPC3 蛋白。 36 名血清 GPC3 阳性患者中，有 27 名血清 5-S-半胱氨酰多巴和黑色素瘤抑制活性（众所周知的黑色素瘤肿瘤标志物）均为阴性。血清GPC3阳性率(39.6%)显着高于5-S-半胱氨酰多巴(26.7%)和黑色素瘤抑制活性(20.9%)。令人惊讶的是，我们甚至在 0 期原位黑色素瘤患者中也检测到了血清 GPC3。 0、I、II期血清GPC3阳性率（44.4%、40.0%、47.6%）显着高于5-S-半胱氨酸多巴（0.0%、8.0%、10.0%）。还观察到，手术切除黑色素瘤后，11 名患者的血清中 GPC3 蛋白消失。结论：GPC3 显然是一种新的肿瘤标志物，可用于诊断黑色素瘤，尤其是在疾病的早期阶段。
Purpose: We reported recently the novel tumor marker glypican-3 (GPC3) for hepatocellular carcinoma. In the present study, we investigated the expression of GPC3 in human melanoma cell lines and tissues and asked whether GPC3 could be a novel tumor marker for melanoma.Experimental Design: Expression of GPC3 mRNA and protein was investigated in human melanoma cell lines and tissues using reverse transcription-PCR and immunohistochemical analysis. Secreted GPC3 protein was quantified using ELISA in culture supernatants of melanoma cell lines and in sera from 91 patients with melanoma and 28 disease-free patients after surgical removal of primary melanoma. All of the subjects were Japanese nationals.Results: In >80% of melanoma and melanocytic nevus, there was evident expression of GPC3 mRNA and protein. Furthermore, GPC3 protein was evidenced in sera of 39.6% (36 of 91) of melanoma patients but not in sera from subjects with large congenital melanocytic nevus (0 of 5) and from healthy donors (0 of 60). Twenty-seven of 36 serum GPC3-positive patients were negative for both serum 5-S-cysteinyl-dopa and melanoma-inhibitory activity, well-known tumor markers for melanoma. The positive rate of serum GPC3 (39.6%) was significantly higher than that of 5-S-cysteinyldopa (26.7%) and of melanoma-inhibitory activity (20.9%). Surprisingly, we detected serum GPC3 even in patients with stage 0 in situ melanoma. The positive rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%, and 47.6%) was significantly higher than that of 5-S-eysteinyldopa (0.0%, 8.0%, and 10.0%). Also observed was the disappearance of GPC3 protein in sera from 11 patients after surgical removal of the melanoma.Conclusions: GPC3 is apparently a novel tumor marker useful for the diagnosis of melanoma, especially in early stages of the disorder.