Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK.
Department of Pathology, Faculty of Medicine, University of Tripoli, Tripoli, Libya.
Breast Cancer Res Treat. 2020 May;181(1):1-12. doi: 10.1007/s10549-020-05586-6. Epub 2020 Mar 21.
Breast cancer (BC) is a heterogeneous disease consisting of various subtypes, with different prognostic and therapeutic outcomes. The amino acid transporter, SLC7A8, is overexpressed in oestrogen receptor-positive BC. However, the consequence of this overexpression, in terms of disease prognosis, is still obscure. This study aimed to evaluate the biological and prognostic value of SLC7A8 in BC with emphasis on the intrinsic molecular subtypes.
SLC7A8 was assessed at the genomic, using METABRIC data (n = 1980), and proteomic, using immunohistochemistry and TMA (n = 1562), levels in well-characterised primary BC cohorts. SLC7A8 expression was examined with clinicopathological parameters, molecular subtypes, and patient outcome.
SLC7A8 mRNA and SLC7A8 protein expression were strongly associated with good prognostic features, including small tumour size, low tumour grade, and good Nottingham Prognostic Index (NPI) (all P < 0.05). Expression of SLC7A8 mRNA was higher in luminal tumours compared to other subtypes (P < 0.001). High expression of SLC7A8 mRNA and SLC7A8 protein was associated with good patient outcome (P ≤ 0.001) but only in the low proliferative ER+/luminal A tumours (P = 0.01). In multivariate analysis, SLC7A8 mRNA and SLC7A8 protein were independent factors for longer breast cancer specific survival (P = 0.01 and P = 0.03), respectively.
SLC7A8 appears to play a role in BC and is a marker for favourable prognosis in the most predominant, ER+ low proliferative/luminal A, BC subtype. Functional assessment is necessary to reveal the specific role played by SLC7A8 in ER+ BC.
乳腺癌（BC）是一种异质性疾病，由各种亚型组成，具有不同的预后和治疗结果。氨基酸转运蛋白 SLC7A8 在雌激素受体阳性 BC 中过度表达。然而，这种过度表达在疾病预后方面的后果仍然不清楚。本研究旨在评估 SLC7A8 在 BC 中的生物学和预后价值，并特别强调内在的分子亚型。
使用 METABRIC 数据（n=1980）评估 SLC7A8 的基因组水平，并使用免疫组织化学和 TMA（n=1562）评估 SLC7A8 的蛋白质水平，对经过充分特征描述的原发性 BC 队列进行评估。检查 SLC7A8 表达与临床病理参数、分子亚型和患者预后的关系。
SLC7A8 mRNA 和 SLC7A8 蛋白表达与良好的预后特征强烈相关，包括肿瘤体积小、肿瘤分级低和良好的诺丁汉预后指数（NPI）（均 P<0.05）。与其他亚型相比，SLC7A8 mRNA 在 luminal 肿瘤中表达更高（P<0.001）。SLC7A8 mRNA 和 SLC7A8 蛋白的高表达与患者的良好预后相关（P≤0.001），但仅在低增殖性 ER+/luminal A 肿瘤中（P=0.01）。在多变量分析中，SLC7A8 mRNA 和 SLC7A8 蛋白分别是乳腺癌特异性生存时间延长的独立因素（P=0.01 和 P=0.03）。
SLC7A8 似乎在 BC 中发挥作用，是 ER+ 低增殖/luminal A 型 BC 最主要的预后良好标志物。需要进行功能评估以揭示 SLC7A8 在 ER+ BC 中的具体作用。
