Calderón-González Karla Grisel, Valero Rustarazo Ma Luz, Labra-Barrios Maria Luisa, Bazán-Méndez César Isaac, Tavera-Tapia Alejandra, Herrera-Aguirre Maria Esther, Sánchez del Pino Manuel M, Gallegos-Pérez José Luis, González-Márquez Humberto, Hernández-Hernández Jose Manuel, León-Ávila Gloria, Rodríguez-Cuevas Sergio, Guisa-Hohenstein Fernando, Luna-Arias Juan Pedro
Doctorado en Ciencias Biológicas, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina, Iztapalapa, C.P. 09340, México, D. F., México.
Unidad de Proteómica, Centro de Investigación Príncipe Felipe, C/Rambla del Saler 16, 46012 Valencia, España.
J Proteomics. 2015 Jun 21;124:50-78. doi: 10.1016/j.jprot.2015.04.018. Epub 2015 Apr 24.
Breast cancer is the principal cancer in women worldwide. Although there are serum tumor markers such as CEA and HER2, they are detected in advanced stages of the disease and used as progression and recurrence markers. Therefore, there is a necessity for the identification of new markers that might lead to an early detection and also provide evidence of an effective treatment. The aim of this work was to determine the differential protein expression profiles of four breast cancer cell lines in comparison to a normal control cell line by iTRAQ labelling and tandem mass spectrometry, in order to identify putative biomarkers of the disease. We identified 1,020 iTRAQ-labelled polypeptides with at least one peptide identified with more than 95% in confidence. Overexpressed polypeptides in all cancer cell lines were 78, whilst the subexpressed were 128. We categorised them with PANTHER program into biological processes, being the metabolic pathways the most affected. We detected six groups of proteins with the STRING program involved in DNA topology, glycolysis, translation initiation, splicing, pentose pathway, and proteasome degradation. The main subexpressed protein network included mitochondrial proteins involved in oxidative phosphorylation. We propose BAG6, DDX39, ANXA8 and COX4 as putative biomarkers in breast cancer.
We report a set of differentially expressed proteins in the MCF7 and T47D (Luminal A), MDA-MB-231 (Claudin low) and SK-BR-3 (HER2(+)) breast cancer cell lines that have not been previously reported in breast cancer disease. From these proteins, we propose BAG6, DDX39, ANXA8 and COX4 as putative biomarkers in breast cancer. On the other hand, we propose sets of unique polypeptides in each breast cancer cell line that can be useful in the classification of different subtypes of breast cancer.
乳腺癌是全球女性中最主要的癌症。尽管存在血清肿瘤标志物，如癌胚抗原（CEA）和人表皮生长因子受体2（HER2），但它们在疾病晚期才能被检测到，并用作病情进展和复发的标志物。因此，有必要鉴定新的标志物，这些标志物可能有助于早期检测，也能为有效治疗提供证据。本研究的目的是通过同位素标记相对和绝对定量（iTRAQ）标记及串联质谱法，确定四种乳腺癌细胞系与正常对照细胞系相比的差异蛋白质表达谱，以鉴定该疾病的潜在生物标志物。我们鉴定出1020个经iTRAQ标记的多肽，其中至少有一个肽段的鉴定置信度超过95%。所有癌细胞系中过表达的多肽有78种，低表达的有128种。我们使用PANTHER程序将它们归类到生物过程中，其中代谢途径受影响最大。我们用STRING程序检测到六组参与DNA拓扑结构、糖酵解、翻译起始、剪接、戊糖途径和蛋白酶体降解的蛋白质。主要的低表达蛋白质网络包括参与氧化磷酸化的线粒体蛋白质。我们提出BAG6、DDX39、膜联蛋白8（ANXA8）和细胞色素c氧化酶亚基4（COX4）作为乳腺癌的潜在生物标志物。
我们报告了在MCF7和T47D（腔面A型）、MDA - MB - 231（紧密连接蛋白低表达型）和SK - BR - 3（HER2阳性型）乳腺癌细胞系中一组差异表达的蛋白质，这些蛋白质在乳腺癌疾病中此前尚未有报道。从这些蛋白质中，我们提出BAG6、DDX39、ANXA8和COX4作为乳腺癌的潜在生物标志物。另一方面，我们提出了每个乳腺癌细胞系中独特的多肽组，这些多肽组可用于不同亚型乳腺癌的分类。
