Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, U.S.A.
Cancer Genomics Proteomics. 2019 May-Jun;16(3):147-153. doi: 10.21873/cgp.20120.
Infiltrating lobular carcinoma (ILC) is the second most common histologicaI subtype of breast cancer, accounting for 10% of all cases. ILC has a characteristic genomic profile. ILC shows a high frequency of cadherin 1 (CDH1) mutations, along with loss of phosphatase and tensin homolog (PTEN), activation of alpha serine/threonine kinase (AKT), and mutations in T-box transcription factor (TBX3) and forkhead box protein A1 (FOXA1). We suspected that another gene, von Willebrand factor (VWF), might also be part of the profile, since coagulation tests reveal significant differences in patients with breast cancer.
For newly-diagnosed breast cancer, the association between VWF and histology in the GDC Breast Cancer dataset in The Cancer Genome Atlas (TCGA) was evaluated. The following were used to access and analyze the data: Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/); Xena browser (https://xenabrowser.net); cBioportal (http://cbioportal.org); Oncomine (https://oncomine.org); and Prediction Analysis of Microarray 50 (PAM50).
Patients with ILC had higher VWF RNA expression than patients with infiltrating ductal carcinoma and other histology. The difference of expression was present to the same degree in both pre-menopausal and post-menopausal patients. Nine alterations in VWF and PTEN were significantly co-occurrent. Considering all histologies in 843 samples, Tukey's honest significant difference post hoc test showed that VWF RNA expression of the normal subtype was significantly greater than that of the other subtypes (p<0.001).
Our finding of significantly higher VWF RNA expression in the PAM50 normal (non-basal-like) breast cancer subtype suggests that VWF protein measurement might complement or corroborate PAM50 results. VWF and PAM50 results both suggesting a low risk of recurrence might make the decision whether to give chemotherapy easier, especially if VWF protein were an independent predictor.
浸润性小叶癌（ILC）是乳腺癌的第二大亚型，占所有病例的 10%。ILC 具有独特的基因组特征。ILC 表现出高频的钙黏蛋白 1（CDH1）突变，同时伴有磷酸酶和张力蛋白同源物（PTEN）缺失、α丝氨酸/苏氨酸激酶（AKT）激活以及 T 盒转录因子（TBX3）和叉头框蛋白 A1（FOXA1）突变。我们推测另一个基因，血管性血友病因子（VWF）也可能是该特征的一部分，因为凝血试验显示乳腺癌患者存在显著差异。
在癌症基因组图谱（TCGA）的 GDC 乳腺癌数据集，评估了 VWF 与组织学的新诊断乳腺癌的相关性。我们使用以下方法访问和分析数据：基因组数据共享数据库门户（https://portal.gdc.cancer.gov/）；Xena 浏览器（https://xenabrowser.net/）；cBioPortal（http://cbioportal.org/）；Oncomine（https://oncomine.org/）和预测分析微阵列 50（PAM50）。
ILC 患者的 VWF RNA 表达高于浸润性导管癌和其他组织学类型的患者。这种表达差异在绝经前和绝经后患者中程度相同。VWF 和 PTEN 存在 9 种改变，且显著共存。考虑到 843 例样本中的所有组织学类型，Tukey 诚实显著差异事后检验显示，正常亚型（非基底样）的 VWF RNA 表达明显大于其他亚型（p<0.001）。
我们发现 PAM50 正常（非基底样）乳腺癌亚型的 VWF RNA 表达显著升高，这表明 VWF 蛋白测量可能补充或证实 PAM50 结果。VWF 和 PAM50 结果均提示复发风险低，这可能使是否给予化疗的决策更容易，特别是如果 VWF 蛋白是独立的预测因素。
