Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer
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Eliana Vanina Elias1,*, Nadia Pereira de Castro1,*, Paulo Henrique Baldan Pineda1,*, Carolina Sens Abuázar1, Cynthia Aparecida Bueno de Toledo Osorio3, Mabel Gigliola Pinilla1, Sabrina Daniela da Silva1, Anamaria Aranha Camargo4,5, Wilson Araujo Silva Jr6, Elisa Napolitano e Ferreira1, Helena Paula Brentani7, Dirce Maria Carraro1,2
1Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
2National Institute of Science and Technology in Oncogenomics (INCITO), São Paulo, SP, Brazil
3Department of Anatomical Pathology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
4Ludwig Institute for Cancer Research, São Paulo, SP, Brazil
5Molecular Oncology Center, Sirio-Libanese Hospital, São Paulo, SP, Brazil
6Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, SP, Brazil
7Institute of Psychiatry-Medical School, University of São Paulo (FMUSP), São Paulo, SP, Brazil
*These authors have contributed equally to this work
Dirce Maria Carraro, email: [email protected]
Keywords: breast cancer, ductal carcinoma in situ progression, gene signature, cellular-based analysis, molecular markers
Received: January 21, 2016 Accepted: September 20, 2016 Published: September 30, 2016
Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients.
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