Izabella Cristina Costa Ferreira, Alinne Tatiane Faria Silva, Letícia Lopes Dantas, Juliana Franco Almeida, Thaise Gonçalves de Araújo, Donizeti Willian Santos, Luiz Ricardo Goulart, Yara Cristina de Paiva Maia


Institution: Universidade Federal de Uberlândia

“The focus of this study was to determine the gene expression profile of cytokeratins (CK) 5, 6, 8, 14 and 18 in peripheral blood of patients with Breast Cancer (BC) and Breast Benign Disease (BBD), aiming its use as a possible diagnosis biomarker. Women who underwent breast surgery were included in the BC or BBD group. After RNA extraction from peripheral blood, cDNA was obtained by reverse transcription and amplified by Polymerase Chain Reaction (PCR) and this process was confirmed by electrophoresis. The gene expression profile of CK5, CK6, CK8, CK14 and CK18 was determined by real time PCR. Concerning the clinical characterization, most of the analyzed patients showed intermediate tumor size and histological grade, less aggressive subtype (luminal), without evident metastasis. Only CK8 and CK18 presented higher levels of gene expression in the BC group compared to BBD group (p=0.037 and p=0.048, respectively). Among the analyzed CKs, the CK8 presented odds ratio (O.R.) greater than 3.00 and p<0.05. The main model for CTCs formation is epithelial-mesenchymal transition (EMT), but we refute this mechanism because the higher transcriptional levels in BC were CKs expressed in more differentiated layer of the mammary epithelium (CK8 and CK18). According to the definition of EMT, circulating tumor cells (CTC) would not express CK or would express CK of the most undifferentiated layer (CK5, CK14 and CK6), which was not found in the study. One possible mechanism for the CTCs formation affirms that the tumor is composed of different cell types with different capacities to migrate and invade secondary sites. The functions of CK8/CK18 dimer are still controversial, but the maintenance of its expression in tumorigenesis can result from the same oncogene activation pathway. Among the analyzed CKs, only CK8 could be used as a serum biomarker for diagnosis and inserted in clinical routine.

Keywords: Breast Cancer; Cytokeratins; Circulating Tumor Cells; Biomarker”