Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.
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ABSTRACT:
SUBMITTER: Song G
PROVIDER: S-EPMC7140215 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Identification of aberrant gene expression during breast ductal carcinoma <i>in situ</i> progression to invasive ductal carcinoma.
Song Guiqin G He Lang L Yang Xiaolin X Yang Yan Y Cai Xiaoming X Liu Kang K Feng Gang G
The Journal of international medical research 20190203 1
Similar Datasets
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression. Tumor and matching stroma were profiled for 9 DCIS patients, 10 IBC patients, and 3 normal breast. Differential gene expression was evaluated for paired normal stroma versus normal epitelium samples, paired DCIS stroma versus DCIS epitelium samples, paired IBC stroma versus IBC epitelium, IBC stroma versus DCIS stroma, and IBC epithelium versus DCIS epithelium.
| S-ECPF-GEOD-33692 | biostudies-other
Project description:Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that is separated from the breast stroma by an intact layer of basement membrane and myoepithelial cells. DCIS is a non-obligate precursor of invasive breast cancer, and up to 40% of these lesions progress to invasive disease if untreated. Currently, it is not possible to predict accurately which DCIS would be more likely to progress to invasive breast cancer as neither the significant drivers of the invasive transition have been identified, nor has the clinical utility of tests predicting the likelihood of progression been demonstrated. Although molecular studies have shown that qualitatively, synchronous DCIS and invasive breast cancers are remarkably similar, there is burgeoning evidence to demonstrate that intra-tumor genetic heterogeneity is observed in a subset of DCIS, and that the process of progression to invasive disease may constitute an 'evolutionary bottleneck', resulting in the selection of subsets of tumor cells with specific genetic and/or epigenetic aberrations. Here we review the clinical challenge posed by DCIS, the contribution of the microenvironment and genetic aberrations to the progression from in situ to invasive breast cancer, the emerging evidence of the impact of intra-tumor genetic heterogeneity on this process, and strategies to combat this heterogeneity.
| S-EPMC5528459 | biostudies-other
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression. Tumor and matching stroma were profiled for 9 DCIS patients, 10 IBC patients, and 3 normal breast. Differential gene expression was evaluated for paired normal stroma versus normal epitelium samples, paired DCIS stroma versus DCIS epitelium samples, paired IBC stroma versus IBC epitelium, IBC stroma versus DCIS stroma, and IBC epithelium versus DCIS epithelium.
2012-03-31 | E-GEOD-33692 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression.
2012-04-01 | GSE33692 | GEO
Project description:The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. SIGNIFICANCE: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.
| S-EPMC6513674 | biostudies-literature
Project description:Elucidating the progression mechanism from ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive ductal carcinoma (IDC), remains a critical challenge in oncology. Metabolic profiling of lesions with differential invasiveness may help reveal key drivers underlying DCIS progression. This study employed mass spectrometry imaging to delineate the small-molecule metabolic profiles of DCIS, DCIS with synchronous IDC, and IDC lesions. Key metabolic alterations driving DCIS-to-IDC progression were identified, including elevated fatty acid biosynthesis in tumor tissues. Comparative analyses revealed that IDC exhibited significantly higher accumulation of polyunsaturated fatty acids (PUFAs) than DCIS (P<0.05), consistent with immunohistochemical validation showing upregulated fatty acid desaturase 2 expression in IDC. DCIS lesions predominantly accumulated phosphatidylinositols with saturated/monounsaturated acyl chains, while IDC exhibited a marked enrichment of phosphatidylinositols with PUFA (P<0.01). Furthermore, IDC showed significantly reduced levels of antioxidant molecules (taurine, ascorbic acid, glutathione) and the detoxification enzyme glutathione S-transferase mu 2 compared to DCIS (P<0.05), indicating dysregulation of redox homeostasis. Strikingly, DCIS with synchronous IDC displayed metabolic signatures closely aligned with IDC, suggesting its role as a transitional state during malignant progression. These findings indicate that DCIS malignant progression exhibits metabolic dependency on PUFAs/phosphatidylinositols with PUFA and depletion of antioxidants. Therapeutic targeting of PUFA biosynthesis or redox homeostasis regulators may offer novel translational approaches for tracking and intercepting DCIS progression.
2025-03-26 | GSE292487 | GEO
Project description:The underlying mechanism of the progression of ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive breast cancer (IBC), has yet to be elucidated. In IBC, Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide-Like 3B (APOBEC3B) is upregulated in a substantial proportion of cases and is associated with higher mutational load and poor prognosis. However, APOBEC3B expression has never been studied in DCIS. We performed mRNA expression analysis of APOBEC3B in synchronous DCIS and IBC and surrounding normal cells. RNA was obtained from 53 patients. The tumors were categorized based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2) and phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) mutation status. APOBEC3B mRNA levels were measured by RT-qPCR. The expression levels of paired DCIS and adjacent IBC were compared, including subgroup analyses. The normal cells expressed the lowest levels of APOBEC3B. No differences in expression were found between DCIS and IBC. Subgroup analysis showed that APOBEC3B was the highest in the ER subgroups of DCIS and IBC. While there was no difference in APOBEC3B between wild-type versus mutated PIK3CA DCIS, APOBEC3B was higher in wild-type versus PIK3CA-mutated IBC. In summary, our data show that APOBEC3B is already upregulated in DCIS. This suggests that APOBEC3B could already play a role in early carcinogenesis. Since APOBEC3B is a gain-of-function mutagenic enzyme, patients could benefit from the therapeutic targeting of APOBEC3B in the early non-invasive stage of breast cancer.
| S-EPMC6721358 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE41194: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 1) GSE41196: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 2) GSE41197: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 3) GSE41198: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 stroma) GSE41227: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 Epithelial) Refer to individual Series
| S-ECPF-GEOD-41228 | biostudies-other
Project description:Here, we show that SOX11, an embryonic mammary marker that is normally silent in postnatal breast cells, is expressed in many oestrogen receptor-negative preinvasive ductal carcinoma in situ (DCIS) lesions. Mature mammary epithelial cells engineered to express SOX11 showed alterations in progenitor cell populations, including an expanded basal-like population with increased aldehyde dehydrogenase (ALDH) activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 showed increased ALDH activity, which is a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS.com cells that expressed SOX11. Upregulating SOX11 expression in DCIS.com cells led to increased invasive growth both in vitro and when they were injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions formed sooner and tumour growth was augmented in vivo, suggesting that SOX11 contributes to the progression of DCIS to invasive breast cancer. We identified potential downstream effectors of SOX11 during both microinvasive and invasive tumour growth stages, including several with established links to regulation of progenitor cell function and prenatal developmental growth. Our findings suggest that SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features that are likely to progress to invasive breast cancer. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
| S-EPMC5637904 | biostudies-literature
Project description:Molecular mechanisms mediating the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer remain largely unknown. We used gene expression profiling of human DCIS (n = 53) and invasive breast cancer (n = 51) to discover uniquely expressed genes that may also regulate progression. There were 470 total differentially expressed genes (?2-fold; P < 0.05). Elevated expression of genes involved in synthesis and organization of extracellular matrix was particularly prominent in the epithelium of invasive breast cancer. The degree of overlap of the genes with nine similar studies in the literature was determined to help prioritize their potential importance, resulting in 74 showing overlap in ?2 studies (average 3.6 studies/gene; range 2-8 studies). Using hierarchical clustering, the 74-gene profile correctly categorized 96% of samples in this study and 94% of samples from 3 similar independent studies. To study the progression of DCIS to invasive breast cancer in vivo, we introduced human DCIS cell lines engineered to express specific genes into a "mammary intraductal DCIS" xenograft model. Progression of xenografts to invasive breast cancer was dramatically increased by suppressing four genes that were usually elevated in clinical samples of DCIS, including a protease inhibitor (CSTA) and genes involved in cell adhesion and signaling (FAT1, DST, and TMEM45A), strongly suggesting that they normally function to suppress progression. In summary, we have identified unique gene expression profiles of human DCIS and invasive breast cancer, which include novel genes regulating tumor progression. Targeting some of these genes may improve the detection, diagnosis, and therapy of DCIS.
| S-EPMC3899801 | biostudies-literature