Identification of a gene signature for different stages of breast cancer development that could be used for early diagnosis and specific therapy

Charu Kothari; Geneviève Ouellette; Yvan Labrie; Simon Jacob; Caroline Diorio; Francine Durocher

doi:10.18632/oncotarget.26448

Identification of a gene signature for different stages of breast cancer development that could be used for early diagnosis and specific therapy

Oncotarget. 2018 Dec 21;9(100):37407-37420. doi: 10.18632/oncotarget.26448.

Authors

Charu Kothari^{1

2}, Geneviève Ouellette^{1

2}, Yvan Labrie^{1

2}, Simon Jacob^{2

3}, Caroline Diorio^{2

4}, Francine Durocher^{1

2}

Affiliations

¹ Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
² Centre de recherche sur le cancer, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada.
³ Laboratoire de pathologie, Hôpital du Saint-Sacrement, CHU de Québec-Université Laval, Québec, Canada.
⁴ Département de médecine sociale et préventive, Faculté de médecine, Université Laval, Québec, Canada.

Abstract

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 in situ (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 SFRP1 and snoRNAs (especially SNORD115 and SNORD114) 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.

Keywords: breast cancer progression; ductal carcinoma in situ (DCIS); gene signature; human transcriptome array (HTA) analysis; invasive ductal carcinoma (IDC).