Abstract
PurposeDuctal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.MethodsForty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-β downstream pathway.ResultsmiRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFβRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFβRII, especially in cells transfected with both miRNAs.ConclusionmiR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-β activity, leading to early breast cancer carcinogenesis.
Highlights
Ductal carcinoma in situ (DCIS) is a spectrum of pre-invasive lesions consisting of malignant cancer cells that accumulate within the intra-mammary lumen, without accompanying basement membrane invasion of the mammary duct [1]
DCIS is well-known precancerous lesion that could eventually progress to invasive ductal carcinoma (IDC), the underlying mechanism of malignant transformation remains largely unknown
This gap in knowledge is largely due to rare incidence of recurrent DCIS or IDC after effective primary treatment
Summary
Ductal carcinoma in situ (DCIS) is a spectrum of pre-invasive lesions consisting of malignant cancer cells that accumulate within the intra-mammary lumen, without accompanying basement membrane invasion of the mammary duct [1]. DCIS is a precursor of invasive ductal carcinoma (IDC) based on the pathologic continuity of histologic findings [2] and similarity of gene expression profiles during the evolution of breast cancer cells [3]. The current treatment of DCIS is based on surgical resection with a negative margin, followed by adjuvant radiation and hormonal therapy to prevent recurrence. Approximately 10–20% of patients show local recurrence as DCIS or IDC during 15 years of follow-up [6,7,8,9]. Previous studies have reported various clinicopathologic features associated with recurrence as DCIS or IDC
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