Identification of early molecular markers for breast cancer

Abstract

BackgroundThe ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore in silico analyses using an online microarray database were performed.ResultsIn DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry.ConclusionsBy comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.

DEP Domain Containing 1 is a Novel Diagnostic Marker and Prognostic Predictor for Hepatocellular Carcinoma

“…Previous reports have demonstrated that DEPDC1 is up-regulated in bladder cancer (Kanehira et al, 2007), breast cancer (Kretschmer et al, 2011) and lung cancer (Okayama et al, 2012). To our knowledge, our report is the first one showed DEPDC1 up-regulation in HCC.…”

“…Given that DEPDC1 is also up-regulated in bladder cancer (Kanehira et al, 2007), breast cancer (Kretschmer et al, 2011) and lung cancer (Okayama et al, 2012), it is crucial to unveil how DEPDC1 is regulated in future study. Researchers found DEPDC1 was up-regulated in bladder cancer tissues, but undetectable in 24 normal human tissues except in testis (Kanehira et al, 2007), and developed peptide vaccine based on this cancer/testis antigen, which effectively induced peptide-specific cytotoxic T lymphocyte in vivo (Obara et al, 2012).…”

“…A very recent report showed that, in HeLa and MCF-7 cells, DEPDC1 promotes JNK-dependent degradation of MCL1, an anti-apoptotic Bcl-2 family member, and therefore inhibits apoptosis (Sendoel et al, 2014). Several reports in bladder cancer, breast cancer and lung cancer demonstrated that DEPDC1 up-regulation might have important role in tumorigenesis (Kanehira et al, 2007;Harada et al, 2010;Kretschmer et al, 2011;Okayama et al, 2012;Kassambara et al, 2013). However, whether DEPDC1 also plays a pivotal role in hepatocelluar carcinoma progression and what is its clinical significance in HCC patients are still unknown.…”

Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions

“…In addition, the performance of this signature was evaluated in cohorts from three similar independent studies [21][22][23][24]. The discovery of distinct molecular subtypes in DCIS has further validated these lesions as precursors of the different subtypes of invasive breast carcinomas.…”

RRM2 (ribonucleotide reductase M2)

“…Recently Kretschmer and colleagues identified molecular markers for the ductal carcinoma in situ using WAP-TNP8 mouse model. In particular, they identified seven marker genes (RRM2, MUC1, SPP1, FOXM1, EXO1, NUSAP1 and DEPDC1), which were overexpressed at a very early stage of premalignancy and preneoplasia of breast carcinomas (Kretschmer et al, 2011).…”