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多肽-N-乙酰半乳糖胺转移酶-13对乳腺癌预后具有影响。

Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer.

作者信息

Fernandez Eugenia, Ubillos Luis, Elgul Nabila, Festari María Florencia, Mazal Daniel, Pritsch Otto, Alonso Isabel, Osinaga Eduardo, Berois Nora

机构信息

Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay.

Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo 11600, Uruguay.

出版信息

Cancers (Basel). 2021 Nov 10;13(22):5616. doi: 10.3390/cancers13225616.

Abstract

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients' clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

摘要

乳腺癌是一个公共卫生问题,目前是全球第五大致死原因。识别不同的生物学亚型对于临床管理至关重要;因此,病理学家的作用至关重要,并且需要用于免疫组织化学诊断的有用工具。多肽-N-乙酰半乳糖胺转移酶是与癌症行为相关的新兴新型生物标志物,而与某些肿瘤侵袭性相关的GalNAc-T13是一个有趣的候选物。据报道,很少有与天然蛋白质反应且不受固定和石蜡包埋影响的单克隆抗体。这项工作的目的是开发一种有用的抗GalNAc-T13单克隆抗体,并评估其在乳腺癌诊断中的潜在意义。我们评估了6个人类乳腺癌细胞系、338例原发性乳腺肿瘤和48个转移性淋巴结,并寻找将GalNAc-T13表达与患者临床特征和生存相关联的临床意义。我们发现43.8%的病例中GalNAc-T13表达较高,并且观察到转移性淋巴结中的表达明显更高,这与较差的总生存期相关。我们推测了几种可能的分子机制及其影响。我们得出结论,GalNAc-T13可能是乳腺癌中的一种新型生物标志物,可用于常规病理诊断。阐明与侵袭性相关的分子机制应有助于理解GalNAc-T13在乳腺癌生物学中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e88a/8616257/1007e8296fd4/cancers-13-05616-g001.jpg

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