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分析分子标志物作为乳腺癌淋巴结受累的预测因素

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

作者信息

Paula Luciana Marques, De Moraes Luis Henrique Ferreira, Do Canto Abaeté Leite, Dos Santos Laurita, Martin Airton Abrahão, Rogatto Silvia Regina, De Azevedo Canevari Renata

机构信息

Laboratory of Molecular Biology of Cancer, Institute of Research and Development (IP&D), University of Vale do Paraíba, São José dos Campos, 12244-000 São Paulo, Brazil.

Mastology Department, San Francisco Assis Hospital, Jacareí, 12311-200 São Paulo, Brazil.

出版信息

Oncol Lett. 2017 Jan;13(1):488-496. doi: 10.3892/ol.2016.5438. Epub 2016 Nov 28.

Abstract

Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with the development of distant metastases, they did not have predictive potential.

摘要

淋巴结状态是乳腺癌最重要的独立预后因素。鉴定分子标志物将能够对大量不需要进行淋巴结手术评估的患者与需要进行该手术评估的患者进行分层,从而得出更准确的预后。然而,到目前为止,所报道的研究都是初步的且存在争议,尽管已经评估了数百种标志物,但其中很少有用于乳腺癌治疗或预后的临床实践。本研究的目的是确定在先前的一项微阵列研究中被描述为乳腺癌预后标志物的蛋白磷酸酶Mg2+/Mn2+依赖性1D、β-1,3-N-乙酰葡糖胺基转移酶、神经前体细胞表达且发育下调9、抑制素、磷酸肌醇-3-激酶调节亚基5(PIK3R5)、磷脂酰肌醇-5-磷酸4-激酶IIα型、TRF1相互作用锚蛋白相关ADP核糖聚合酶2、细胞死亡的BCL2相关激动剂、G2和S期表达1以及PAX相互作用蛋白1基因,是否也是乳腺癌淋巴结受累的预测指标。对淋巴结阴性受累女性(n=27)的原发性乳腺肿瘤组织与淋巴结阳性受累女性(n=23)的原发性肿瘤组织进行了逆转录定量聚合酶链反应分析,并且也对原发性肿瘤和配对的淋巴结转移灶(n=11)进行了该分析。对于所有分析的基因,与淋巴结阴性受累的原发性肿瘤相比,只有PIK3R5基因在淋巴结阳性受累的原发性肿瘤样本中表现出差异表达(P=0.0347)。这些结果表明,PIK3R5基因可能被认为是乳腺癌淋巴结受累的预测指标。尽管本研究中评估的其他基因先前已被确定与远处转移的发生有关,但它们没有预测潜力。

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