Kothari Charu, Ouellette Geneviève, Labrie Yvan, Jacob Simon, Diorio Caroline, Durocher Francine
Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
Centre de recherche sur le cancer, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada.
Oncotarget. 2018 Dec 21;9(100):37407-37420. doi: 10.18632/oncotarget.26448.
Breast cancer (BC) is a heterogeneous disease where the survival rate of patients decreases with progression of the disease. BC usually has a linear progression, classified into normal/benign, atypical ductal hyperplasia (ADH), ductal carcinoma (DCIS), and invasive ductal carcinoma (IDC). This study aimed to identify gene signature for each of these subgroups. We performed human transcriptome array analysis on 5 patient samples from each Normal, ADH, IDC and DCIS and 2 replicates of MCF10A cell line representative of each subgroup. We identified and snoRNAs (especially and ) as the initial regulators of cancer progression, accompanied by significant changes in extracellular matrix organization. Tumor progression to the IDC stage showed upregulation of tumor promoting genes responsible for increased invasion, inflammation, survival in stress environment and metastasis. The gene signatures identified in this study could represent potential biomarkers for each subgroup of breast cancer progression, which could assist in early diagnosis of breast cancer progression as well as treatment interventions. Moreover, these gene signatures could serve in discovery of specific targeted therapies for each subgroup.
乳腺癌（BC）是一种异质性疾病，患者的生存率会随着疾病进展而降低。BC通常呈线性进展，分为正常/良性、非典型导管增生（ADH）、导管原位癌（DCIS）和浸润性导管癌（IDC）。本研究旨在确定这些亚组各自的基因特征。我们对来自正常、ADH、IDC和DCIS的5例患者样本以及代表每个亚组的MCF10A细胞系的2个复制品进行了人类转录组阵列分析。我们鉴定出 和snoRNAs（尤其是 和 ）作为癌症进展的初始调节因子，同时细胞外基质组织也发生了显著变化。肿瘤进展到IDC阶段显示出负责增加侵袭、炎症、应激环境下的生存和转移的促肿瘤基因上调。本研究中鉴定出的基因特征可能代表乳腺癌进展各亚组的潜在生物标志物，这有助于乳腺癌进展的早期诊断以及治疗干预。此外，这些基因特征可用于发现针对每个亚组的特定靶向疗法。
