UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow-disseminated breast cancer cells
UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6 (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow-disseminated breast cancer cells
复制标题
DOI：
10.1002/ijc.21959
复制
发表时间：
2006-09-15
影响因子：
6.4
通讯作者：
Osinaga, Eduardo
中科院分区：
文献类型：
--
作者：
Freire, Teresa;Berois, Nora;Osinaga, Eduardo
对早期乳腺癌患者的播散上皮肿瘤细胞的评估已经引起了相当大的兴趣，因为它可能与不良的临床结果相关。考虑到O-糖基化途径在乳腺癌中经常发生改变，我们开展了这项工作，以评估UDP-N-乙酰-D-氨基半乳糖：多肽N-乙酰半乳糖胺转移酶(ppGalNAe-ts)(催化粘蛋白O-糖基化第一步的糖基转移酶家族)在检测可手术乳腺癌患者骨髓样本中播散细胞的潜在有用性。采用RT-PCR方法，研究了9种酶(ppGalNAc-T1-T9)的基因表达。在乳腺肿瘤表达的ppGalNAc-ts(-T1、T2、T3、-T6和-T7)中，ppGalNAc-T6的特异性最好(对所有健康供者的PBMN细胞样本均为阴性)。因此，我们选择该酶作为进一步研究的目标基因。PGalNAc-T6mRNA在22/25例(95%)乳腺癌标本中表达，在所研究的3种人乳腺癌细胞系(MCF-7、ZR75-1和T47D)中表达，1/30(3%)PBMN细胞中表达，0/19例非癌患者骨髓标本中表达。在61例根治性手术的乳腺癌患者中，有22例(36%)术前骨髓抽吸物ppGalNAc-T6mRNA呈阳性，其中11/34例为I期或II期，无淋巴结转移。在初步的随访评估中，61例患者中有19例复发。PpGalNAc-T6阳性11例(57.9%)。有趣的是，在无淋巴结转移的患者中，骨髓抽吸物ppGalNAc-T6mRNA阳性的患者中有54.5%的患者病情复发，而ppGalNAc-T6mRNA阴性的患者中只有4.3%的患者复发(p=0.014)。这些结果表明ppGalNAc-T6mRNA可以作为乳腺癌细胞播散的分子诊断的特异性标志物。(C)2006年Wiley-Liss，Inc.
The evaluation of disseminated epithelial tumor cells in patients with early stages of breast cancer has generated considerable interest because of its potential association with poor clinical outcome. Considering that O-glycosylation pathways are frequently altered in breast cancer, we performed this work to evaluate the potential usefulness of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAe-Ts) (a family of glycosyltransferases which catalyze the first key step of mucin-type O-glycosylation) to detect disseminated cells in bone marrow samples from patients with operable breast cancer. Using RTPCR assays, we studied the gene expression of 9 enzymes (ppGalNAc-T1-T9). Among the ppGalNAc-Ts expressed by breast tumors (-T1, T2, T3, -T6 and -T7), the best specificity (negative results on all PBMN cell samples from healthy donors) was shown for ppGalNAc-T6. Thus, we selected this enzyme as a target gene for further evaluation. ppGalNAc-T6 mRNA was found in 22/25 (95%) breast cancer samples, in all 3 human breast cancer cell lines evaluated (MCF-7, ZR75-1 and T47D), in 1/30 (3%) PBMN cells and 0/19 bone marrow samples obtained from patients without cancer. Using this method, 22/61 (36%) patients with breast cancer, who underwent curative surgery, showed positive ppGalNAc-T6 mRNA in bone marrow aspirates obtained prior to surgery, including 11/34 patients with stage-I or -II, without histopathological lymph node involvement. In a preliminary follow-up evaluation, 19/61 patients experienced recurrence of the disease. ppGalNAc-T6 was positive in 11/19 (57.9%) of these patients. Interestingly, in the group of patients without lymph node involvement, disease recurrence was observed in 54.5% of patients who showed ppGalNAc-T6 mRNA-positive bone marrow aspirates and only in 4.3% of patients when ppGalNAc-T6 was negative (p = 0.014). These results indicate that ppGalNAc-T6 mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cells dissemination. (c) 2006 Wiley-Liss, Inc.