Vitiello Glauco Akelinghton Freire, Amarante Marla Karine, Oda Julie Massayo Maeda, Hirata Bruna Karina Banin, de Oliveira Carlos Eduardo Coral, Campos Clodoaldo Zago, de Oliveira Karen Brajão, Guembarovski Roberta Losi, Watanabe Maria Angelica Ehara
Department of Pathological Sciences, Biological Sciences Center, Londrina State University, Londrina, PR, Brazil.
Department of Clinical Research, Londrina Cancer Hospital, Londrina, PR, Brazil; Department of Clinical Medicine, Health Sciences Center, Londrina State University, Londrina, PR, Brazil.
Cytokine. 2020 Mar 28;130:155079. doi: 10.1016/j.cyto.2020.155079.
Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that acts in a context-dependent manner. In breast cancer (BC) this cytokine exerts subtype- and stage-specific roles, inhibiting poorly aggressive tumors while enhances the invasive potential of highly aggressive cancers. Single-nucleotide polymorphisms (SNPs) affecting TGFβ1 production largely reflect this pattern of association, but studies investigating systemic TGFβ1 levels in BC patients and their association with clinical features or SNPs produced conflicting conclusions. Therefore, the present work investigated plasmatic TGFβ1 levels through enzyme linked immunosorbent assay (ELISA) in 341 individuals previously genotyped for four TGFB1 SNPs [G-800A (rs1800468), C-509T (rs1800469), T29C (rs1800470) and G74C (rs1800471)], encompassing 184 neoplasia-free women with clinical information regarding health status, 113 treatment-free pre-surgery BC patients and 44 treated BC patients. Results have shown that TGFβ1 levels varied greatly in function of health status in neoplasia-free women, and disease-free individuals had higher TGFβ1 levels than both treatment-free or treated BC patients. There was no correlation between TGFβ1 with clinicopathological features in treatment-free BC general group, but it was negatively correlated with tumor size in luminal-B-HER2 patients and with histopathological grade in triple-negative group. Also, TGFB1 ACTG haplotype (from G-800A to G74C) was associated with decreased TGFβ1 levels compared to the reference GCTG haplotype, and regression analyses showed that this association was independent of age, health status or BC diagnosis. In conclusion, several factors may influence TGFβ1 levels, and ACTG haplotype seems to be an important factor regulating TGFβ1 production.
转化生长因子β1（TGFβ1）是一种多效细胞因子，其作用具有上下文依赖性。在乳腺癌（BC）中，这种细胞因子发挥着亚型和阶段特异性作用，抑制侵袭性较弱的肿瘤，同时增强高侵袭性癌症的侵袭潜力。影响TGFβ1产生的单核苷酸多态性（SNP）在很大程度上反映了这种关联模式，但研究BC患者全身TGFβ1水平及其与临床特征或SNP的关联得出了相互矛盾的结论。因此，本研究通过酶联免疫吸附测定（ELISA）对341名个体的血浆TGFβ1水平进行了调查，这些个体先前已对四个TGFB1 SNP [G - 800A（rs1800468）、C - 509T（rs1800469）、T29C（rs1800470）和G74C（rs1800471）]进行了基因分型，其中包括184名无肿瘤的女性，她们有关于健康状况的临床信息，113名未经治疗的术前BC患者和44名接受过治疗的BC患者。结果表明，在无肿瘤的女性中，TGFβ1水平因健康状况而有很大差异，无病个体的TGFβ1水平高于未经治疗或接受过治疗的BC患者。在未经治疗的BC总体组中，TGFβ1与临床病理特征之间没有相关性，但在腔面B - HER2患者中与肿瘤大小呈负相关，在三阴性组中与组织病理学分级呈负相关。此外，与参考GCTG单倍型相比，TGFB1 ACTG单倍型（从G - 800A到G74C）与TGFβ1水平降低有关，回归分析表明这种关联独立于年龄、健康状况或BC诊断。总之，几个因素可能影响TGFβ1水平，ACTG单倍型似乎是调节TGFβ1产生的一个重要因素。
