Assessment of messenger RNA of beta 1-->4-N-acetylgalactosaminyl-transferase as a molecular marker for metastatic melanoma.
Assessment of messenger RNA of beta 1-->4-N-acetylgalactosaminyl-transferase as a molecular marker for metastatic melanoma.
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发表时间：
1998-02
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通讯作者：
C. Kuo;P. Bostick;R. Irie;D. Morton;A. Conrad;D. B. Hoon
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作者：
C. Kuo;P. Bostick;R. Irie;D. Morton;A. Conrad;D. B. Hoon
神经节苷脂GM 2 [GalNAc β 1-4（NeuAc α 2-3）Gal β 1-4Glc β 1-1Cer]和GD 2 [GalNAc β 1-4（NeuAc α 2- 8 NeuAc α 2-3）Gal β 1-4Glc β 1-1Cer]是细胞表面肿瘤相关抗原，已被证明是人类恶性黑素瘤进展的重要标志物。这些糖脂抗原在黑色素瘤组织上的表达可以通过免疫组织化学或生物化学分析来评估。然而，这些方法对于测试血液或组织活检中的转移性黑素瘤细胞在逻辑上不实用或不敏感。在本研究中，我们假设参与GM 2和GD 2合成的酶β 1->4-N-乙酰氨基半乳糖转移酶（β 1->4GalNac-T）可以作为检测隐匿性转移性黑色素瘤的有用标志物。建立了检测β 1->4GalNac-T mRNA表达的逆转录PCR和Southern印迹法。在所有13个测试的黑素瘤细胞系中检测到β 1->4GalNac-T mRNA。淋巴结和不同器官部位的转移性黑色素瘤以不同水平表达β 1-->4GalNac-T mRNA。逆转录PCR检测的灵敏度为1 ng的总RNA提取的肿瘤标本和约5黑色素瘤细胞在20万正常供体外周血淋巴细胞。在对来自126名黑色素瘤患者的血液进行评估时，在晚期黑色素瘤和显示出更侵袭性肿瘤进展的患者中更频繁地发现β 1->4GalNac-T mRNA。正常供体血液样品（n = 37）对于β 1->4GalNac-T mRNA表达均为阴性。这些结果表明，β 1->4GalNac-T mRNA是一种有前途的检测黑色素瘤细胞，表征抗原表达和监测肿瘤进展的分子标志物。
Gangliosides GM2 [GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer] and GD2 [GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer] are cell surface tumor-associated antigens and have been demonstrated to be important markers of human malignant melanoma progression. Expression of these glycolipid antigens on melanoma tissues can be assessed by immunohistochemistry or biochemical analysis. These methodologies, however, are not logistically practical or sensitive for testing metastatic melanoma cells in blood or in tissue biopsies. In the present study, we hypothesized that the enzyme involved in GM2 and GD2 synthesis, beta 1-->4-N-acetylgalactosaminyltransferase (beta 1-->4GalNac-T), can be a useful marker for detection of occult metastatic melanoma. A reverse transcription PCR and Southern blot assay to detect beta 1-->4GalNac-T mRNA expression was developed. Beta 1-->4GalNac-T mRNA was detected in all 13 melanoma cell lines tested. Metastatic melanoma of lymph nodes and different organ sites expressed beta 1-->4GalNac-T mRNA at various levels. Detection sensitivity of the reverse transcription PCR assay was 1 ng of total RNA extracted from tumor specimens and approximately 5 melanoma cells in 20 million normal donor peripheral blood lymphocytes. In assessment of blood from 126 melanoma patients, beta 1-->4GalNac-T mRNA was more frequently found in advanced-stage melanomas and in patients showing more aggressive tumor progression. Normal donor blood samples (n = 37) were all negative for beta 1-->4GalNac-T mRNA expression. These results suggest that beta 1-->4GalNac-T mRNA is a promising molecular marker for detecting melanoma cells, characterizing antigen expression, and monitoring tumor progression.