Cancer cell redirection biomarker discovery using a mutual information approach

Roche, Kimberly; Feltus, F. Alex; Park, Jang Pyo; Coissieux, Marie–May; Chang, Chenyan; Chan, Vera B. S.; Bentires‐Alj, Mohamed; Booth, Brian W.

doi:10.1371/journal.pone.0179265

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…Cancer cell redirection was previously shown using mouse mammary cancer-derived cell lines, triple negative breast cancer cell lines, and embryonic carcinoma cells [3][4][5]. When incorporated into growing ductal trees, stem cell niches direct which phenotype cells will assume during growth [3,6,[11][12][13][14][15][16]. Analogous results are shown here for human HER2 + breast cancer cells.…”

Section: Discussionsupporting

confidence: 78%

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Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using in vivo and in vitro models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either in vivo or in vitro, they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.

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Section: Discussionsupporting

confidence: 78%

“…We have developed and validated an in vitro model of cancer cell redirection using mouse mammary epithelial cells and mouse mammary tumor cells [6,15,16]. The mammary tumor cell lines redirected were derived from tumors that developed in MMTV-neu transgenic female mice.…”

Section: Human Her2 + Breast Cancer Cells Are Redirected In Vitromentioning

confidence: 99%

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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“…There is also an attempt to use RNA profiling data using differential expression to assess if these data "are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state" [31].…”

Section: Microbesmentioning

confidence: 99%

Microbiome and morbid obesity increase pathogenic stimulus diversity

Brücher

Jamall

2019

4open

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The microbiome, the relationship between environmental factors, a high-fat diet, morbid obesity, and host response have been associated with cancer, only a small fraction of which (<10%) are genetically triggered. This nongenetic association is underpinned by a worldwide increase in morbid obesity, which is associated with both insulin resistance and chronic inflammation. The connection of the microbiome and morbid obesity is reinforced by an approximate shift of about 47% in the estimated total number of bacteria and an increase from 38,000,000,000,000 in a reference man to 56,000,000,000,000 in morbid obesity leading to a disruption of the microbial ecology within the gut. Humans contain 6,000,000,000 microbes and more than 90% of the cells of the human body are microorganisms. Changes in the microflora of the gut are associated with the polarization of ion channels by butyrate, thereby influencing cell growth. The decrease in the relative proportion of Bacteroidetes together with a change in the fermentation of carbohydrates by bacteria is observed in morbid obesity. The disruption of homeostasis of the microflora in the obese changes signaling and crosstalk of several pathways, resulting in inflammation while suppressing apoptosis. The interactions between the microbiome and morbid obesity are important to understand signaling and crosstalk in the context of the progression of the six-step sequence of carcinogenesis. This disruption of homeostasis increases remodeling of the extracellular matrix and fibrosis followed by the none-resolvable precancerous niche as the internal pathogenic stimuli continue. The chronic stress explains why under such circumstances there is a greater proclivity for normal cells to undergo the transition to cancer cells.

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“…Information theory has provided a theoretical basis in many data analysis and machine learning tasks since it was proposed for communication and compression perspectives [ 18 , 19 ]. In particular, mutual information (MI) has been a metric widely applied for extracting significant variables from high dimensional data, including gene expression and sequencing data [ 20 , 21 ]. Since it is defined with the entropy of random variables similar to the other information-theoretical methods, such as Kullback–Leibler divergence (KL-divergence), MI formulates the conditional independency between two random variables.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Identification of Discriminative Genetic Variations in Beef and Dairy Cattle via an Information-Theoretic Approach

Kim

2020

Genes

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Analyzing the associations between genotypic changes and phenotypic traits on a genome-wide scale can contribute to understanding the functional roles of distinct genetic variations during breed development. We performed a whole-genome analysis of Angus and Jersey cattle breeds using conditional mutual information, which is an information-theoretic method estimating the conditional independency among multiple factor variables. The proposed conditional mutual information-based approach allows breed-discriminative genetic variations to be explicitly identified from tens of millions of SNP (single nucleotide polymorphism) positions on a genome-wide scale while minimizing the usage of prior knowledge. Using this data-driven approach, we identified biologically relevant functional genes, including breed-specific variants for cattle traits such as beef and dairy production. The identified lipid-related genes were shown to be significantly associated with lipid and triglyceride metabolism, fat cell differentiation, and muscle development. In addition, we confirmed that milk-related genes are involved in mammary gland development, lactation, and mastitis-associated processes. Our results provide the distinct properties of Angus and Jersey cattle at a genome-wide level. Moreover, this study offers important insights into discovering unrevealed genetic variants for breed-specific traits and the identification of genetic signatures of diverse cattle breeds with respect to target breed-specific properties.

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Cancer cell redirection biomarker discovery using a mutual information approach

Cited by 8 publications

References 35 publications

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Microbiome and morbid obesity increase pathogenic stimulus diversity

Genome-Wide Identification of Discriminative Genetic Variations in Beef and Dairy Cattle via an Information-Theoretic Approach

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