Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers

Abstract

BackgroundThe transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC.MethodsFifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR.ResultsMultiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P < 0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours.ConclusionWe confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0403-5) contains supplementary material, which is available to authorized users.

Comparative analysis of protein-protein interaction networks in metastatic breast cancer

“…THBS2 gene is also responsible for a co-regulation between cluster 3 and clusters 7–8. Gene expression analysis between ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC) tissues has indicated that the THBS2 gene is up-regulated during the transition between non-invasive to invasive breast cancer [ 66 ]. Furthermore, four other candidate genes SPARC, THY1, IL1B and CXCL8 are reported in this study as the key regulatory genes which can modulate co-regulatory between different clusters in the PPI network of the brain metastasis tumours from breast cancers ( Fig 7C ).…”

Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer

“…The expression of COL10A1 was increased in various solid human tumor tissues, which contributed to tumor vasculature staining [6]. COL10A1 showed an important role in differentiating in situ from invasive breast cancer and characterizing DCIS with a high risk developing IDC [11,15,16]. Additionally, the concentration of COL10A1 in the plasma could be a potential biomarker to discriminate breast cancer patients from those with benign disease [9].…”

GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients

“…It was recently shown that GREM1 can be produced by cancer-associated fibroblasts (CAFs) in breast cancer patients and that CAFs are the main source of GREM1 in colorectal cancer tissue [46, 47]. Of note, GREM1 was one of eight elevated genes shown in cancer cells laser-dissected from invasive breast carcinoma patients compared with cancer cells from ductal carcinoma in situ patients [48], supporting that GREM1 could be expressed by the transformed cancer cells themselves and associated with an invasive phenotype. Taken together, the elevated GREM1 mRNA found in breast cancer biopsies could either come from the cancer cells themselves, or from cells infiltrating the tumor.…”