Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

: Breast cancer is the most common neoplasm, comprising 16% of all women's cancers worldwide. Research of Copper (Cu) concentrations in various body specimens have suggested an association between Cu levels and breast cancer risks. This systematic review and meta-analysis summarize the results of published studies and examine this association. We searched the databases PubMed, Scopus, Web of Science, and Google Scholar and the reference lists of relevant publications. The Standardized Mean Differences (SMDs) between Cu levels in cancer cases and controls and corresponding Confidence Intervals (CIs), as well as I2 statistics, were calculated to examine heterogeneity. Following the specimens used in the original studies, the Cu concentrations were examined in three subgroups: serum or plasma, breast tissue, and scalp hair. We identified 1711 relevant studies published from 1984 to 2017. There was no statistically significant difference between breast cancer cases and controls for Cu levels assayed in any studied specimen; the SMD (95% CI) was -0.01 (-1.06 - 1.03; P = 0.98) for blood or serum, 0.51 (-0.70 - 1.73; P = 0.41) for breast tissue, and -0.88 (-3.42 - 1.65; P = 0.50) for hair samples. However, the heterogeneity between studies was very high (P < 0.001) in all subgroups. We did not find evidence for publication bias (P = 0.91). The results of this meta-analysis do not support an association between Cu levels and breast cancer. However, due to high heterogeneity in the results of original studies, this conclusion needs to be confirmed by well-designed prospective studies.

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The Expression Pattern of Epidermal Differentiation Marker Keratin 10 in the Normal Human Breast and Breast Cancer Cells

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420940220 ◽

2020 ◽

Vol 68 (8) ◽

pp. 561-570

Author(s):

Jiyoung Kim ◽

René Villadsen

Keyword(s):

Breast Cancer ◽

Expression Pattern ◽

Breast Tissue ◽

Normal Breast ◽

Epidermal Differentiation ◽

Breast Cancer Patients ◽

Human Breast ◽

Normal Human Breast ◽

Differentiation Marker ◽

Breast Gland

Cells of the human breast gland express an array of keratins, of which some are used for characterizing both normal and neoplastic breast tissue. However, the expression pattern of certain keratins has yet to be detailed. Here, the expression of a differentiation marker of epidermal epithelium, keratin 10 (K10), was investigated in the human breast gland. While in normal breast tissue generally less than 1% of luminal epithelial cells expressed K10, in women >30 years of age glandular structures with K10-positive (K10pos) cells were found at higher frequency than in younger women. K10pos cells belong to a mature luminal compartment as they were negative for cKIT, positive for Ks20.8, and mostly non-cycling. In breast cancer, around 16% of primary breast carcinomas tested were positive for K10 by immunohistochemistry. Interestingly, K10pos tumor cells generally exhibit features of differentiation similar to their normal counterparts. Although this suggests that K10 is a marker of tumor differentiation, data based on gene expression analysis imply that high levels of K10 dictate a worse outcome for breast cancer patients. These findings can form the basis of future studies that should unravel which role K10 may play as a marker of breast cancer:

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Accelerated aging in normal breast tissue of women with breast cancer

Breast Cancer Research ◽

10.1186/s13058-021-01434-7 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Shoghag Panjarian ◽

Jozef Madzo ◽

Kelsey Keith ◽

Carolyn M. Slater ◽

Carmen Sapienza ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Anomaly Detection ◽

Breast Tissue ◽

Preventive Intervention ◽

Normal Breast Tissue ◽

Accelerated Aging ◽

Normal Breast ◽

Age Related ◽

Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

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Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue

Endocrine Related Cancer ◽

10.1677/erc.1.01165 ◽

2006 ◽

Vol 13 (2) ◽

pp. 617-628 ◽

Cited By ~ 51

Author(s):

C L Wilson ◽

A H Sims ◽

A Howell ◽

C J Miller ◽

R B Clarke

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Proliferation ◽

Breast Tissue ◽

Epithelial Cell Proliferation ◽

Human Breast ◽

Human Breast Tissue ◽

Tissue Microenvironment ◽

Normal Human Breast ◽

Normal Human

Oestrogen (E) is essential for normal and cancer development in the breast, while anti-oestrogens have been shown to reduce the risk of the disease. However, little is known about the effect of E on gene expression in the normal human breast, particularly when the epithelium and stroma are intact. Previous expression profiles of the response to E have been performed on tumour cell lines, in the absence of stroma. We investigated gene expression in normal human breast tissue transplanted into 9–10-week-old female athymic nude (Balb/c nu/nu) mice. After 2 weeks, when epithelial proliferation is minimal, one-third of the mice were treated with 17β-oestradiol (E2) to give human luteal-phase levels in the mouse, which we have previously shown to induce maximal epithelial cell proliferation. RNA was isolated from treated and untreated mice, labelled and hybridized to Affymetrix HG-U133A (human) GeneChips. Gene expression levels were generated using BioConductor implementations of the RMA and MAS5 algorithms. E2 treatment was found to represent the largest source of variation in gene expression and cross-species hybridization of mouse RNA from xenograft samples was demonstrated to be negligible. Known E2-responsive genes (such as TFF1 and AREG), and genes thought to be involved in breast cancer metastasis (including mammoglobin, KRT19 and AGR2), were upregulated in response to E treatment. Genes known to be co-expressed with E receptor α in breast cancer cell lines and tumours were both upregulated (XBP-1 and GREB1) and downregulated (RARRES1 and GATA3). In addition, genes that are normally expressed in the myoepithelium and extracellular matrix that maintain the tissue microenvironment were also differentially expressed. This suggests that the response to oestrogen in normal breast is highly dependent upon epithelial–stromal/myoepithelial interactions which maintain the tissue microenvironment during epithelial cell proliferation.

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