Zheng Dandan, Jiang Chengwei, Yan Ning, Miao Yayun, Wang Keren, Gao Ge, Jiao Yan, Zhang Xiangkai, He Miao, Yang Zhaoying
Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, People's Republic of China.
Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China.
Onco Targets Ther. 2020 Dec 8;13:12649-12659. doi: 10.2147/OTT.S265324. eCollection 2020.
Wntless (Wls) is an essential protein that is necessary for the secretion of Wnt proteins. While numerous researches have demonstrated that aberrations in Wnt/β-catenin expression lead to tumorigenesis and progression in many cancer types, the effects of Wls in breast cancer (BC) are less studied.
The mRNA and protein expression of Wls in BC cell lines were detected by RT-qPCR and Western blot; the protein expression of patient samples was detected by immunohistochemistry (IHC). The associations between Wls expression and clinicopathological factors as well as survival time, including overall survival (OS) and disease-free survival (DFS) were analyzed. Bioinformatics analysis was used to reveal the correlation between Wls genes and associated genes or pathways.
Wls was overexpressed in BC cell lines and tissues. The expression level of Wls was significantly correlated with tumor size, estrogen receptor (ER), progesterone receptor (PR), Ki-67, molecular classification, and follow-up status. Spearman correlation analysis showed that Wls protein expression was negatively correlated with ER and PR, which was confirmed by bioinformatics analysis in mRNA level. However, there were positive relationships with MBNG (modified Black's nuclear grade), tumor size, Ki-67, molecular classification, follow-up, and vital status. Univariate and multivariate analysis showed that Wls was an independent prognostic factor for OS and DFS in BC patients. Moreover, Wls was a significant prognostic indicator of OS and DFS in a hormone receptor-positive (HR+) subgroup. GSEA showed that estrogen and androgen response, as well as epithelial-mesenchymal transition pathways, were up-regulated in the Wls high-expression group.
Overexpression of Wls is a significant marker of worse prognosis in BC and might play a crucial role in the HR+ subgroup.
无翅型MMTV整合位点家族成员8（Wntless，Wls）是一种对Wnt蛋白分泌至关重要的蛋白质。虽然众多研究表明Wnt/β-连环蛋白表达异常会导致多种癌症类型的肿瘤发生和进展，但Wls在乳腺癌（BC）中的作用研究较少。
采用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测Wls在BC细胞系中的mRNA和蛋白表达；采用免疫组织化学（IHC）检测患者样本的蛋白表达。分析Wls表达与临床病理因素以及生存时间（包括总生存期（OS）和无病生存期（DFS））之间的关联。利用生物信息学分析揭示Wls基因与相关基因或通路之间的相关性。
Wls在BC细胞系和组织中过表达。Wls的表达水平与肿瘤大小、雌激素受体（ER）、孕激素受体（PR）、Ki-67、分子分型及随访状态显著相关。Spearman相关性分析显示Wls蛋白表达与ER和PR呈负相关，这在mRNA水平的生物信息学分析中得到证实。然而，与改良布莱克核分级（MBNG）、肿瘤大小、Ki-67、分子分型、随访及生存状态呈正相关。单因素和多因素分析表明，Wls是BC患者OS和DFS的独立预后因素。此外，Wls是激素受体阳性（HR+）亚组OS和DFS的重要预后指标。基因集富集分析（GSEA）显示，雌激素和雄激素反应以及上皮-间质转化通路在Wls高表达组中上调。
Wls过表达是BC预后较差的重要标志物，可能在HR+亚组中起关键作用。
