Oncotarget

Research Papers:

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 and Francine Durocher _

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Oncotarget. 2018; 9:37407-37420. https://doi.org/10.18632/oncotarget.26448

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Abstract

Charu Kothari1,2, Geneviève Ouellette1,2, Yvan Labrie1,2, Simon Jacob2,3, Caroline Diorio2,4 and Francine Durocher1,2

1Département de médecine moléculaire, Faculté de médecine, Université Laval, Québec, Canada

2Centre de recherche sur le cancer, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada

3Laboratoire de pathologie, Hôpital du Saint-Sacrement, CHU de Québec-Université Laval, Québec, Canada

4Département de médecine sociale et préventive, Faculté de médecine, Université Laval, Québec, Canada

Correspondence to:

Francine Durocher, email: Francine.Durocher@crchudequebec.ulaval.ca

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

Received: July 04, 2018    Accepted: November 26, 2018    Published: December 21, 2018

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.


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