Publications by authors named "Dorota Anusewicz"

2 Publications

  • Page 1 of 1

Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.

Front Cell Dev Biol 2020 15;8:592616. Epub 2020 Dec 15.

Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.

The Notch pathway involves evolutionarily conserved signaling regulating the development of the female tract organs such as breast, ovary, cervix, and uterine endometrium. A great number of studies revealed Notch aberrancies in association with their carcinogenesis and disease progression, the management of which is still challenging. The present study is a comprehensive review of the available literature on Notch signaling during the normal development and carcinogenesis of the female tract organs. The review has been enriched with our analyses of the TCGA data including breast, cervical, ovarian, and endometrial carcinomas concerning the effects of Notch signaling at two levels: the core components and downstream effectors, hence filling the lack of global overview of Notch-driven carcinogenesis and disease progression. Phenotype heterogeneity regarding Notch signaling was projected in two uniform manifold approximation and projection algorithm dimensions, preceded by the principal component analysis step reducing the data burden. Additionally, overall and disease-free survival analyses were performed with the optimal cutpoint determination by Evaluate Cutpoints software to establish the character of particular Notch components in tumorigenesis. In addition to the review, we demonstrated separate models of the examined cancers of the Notch pathway and its targets, although expression profiles of all normal tissues were much more similar to each other than to its cancerous compartments. Such Notch-driven cancerous differentiation resulted in a case of opposite association with DFS and OS. As a consequence, target genes also show very distinct profiles including genes associated with cell proliferation and differentiation, energy metabolism, or the EMT. In conclusion, the observed Notch associations with the female tract malignancies resulted from differential expression of target genes. This may influence a future analysis to search for new therapeutic targets based on specific Notch pathway profiles.
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http://dx.doi.org/10.3389/fcell.2020.592616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770115PMC
December 2020

Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling.

Sci Rep 2020 12 3;10(1):21128. Epub 2020 Dec 3.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland.

Lung malignancies comprise lethal and aggressive tumours that remain the leading cancer-related death cause worldwide. Regarding histological classification, lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) account for the majority of cases. Surgical resection and various combinations of chemo- and radiation therapies are the golden standards in the treatment of lung cancers, although the five-year survival rate remains very poor. Notch, Hedgehog, Wnt and Erbb signalling are evolutionarily conserved pathways regulating pivotal cellular processes such as differentiation, proliferation, and angiogenesis during embryogenesis and post-natal life. However, to date, there is no study comprehensively revealing signalling networks of these four pathways in LUSC and LUAD. Therefore, the aim of the present study was the investigation profiles of downstream target genes of pathways that differ between LUSC and LUAD biology. Our results showed a few co-expression modules, identified through weighted gene co-expression network analysis (WGCNA), which significantly differentiated downstream signaling of Notch, ErbB, Hedgehog, and Wnt in LUSC and LUAD. Among co-expressed genes essential regulators of the cell cycle, DNA damage response, apoptosis, and proliferation have been found. Most of them were upregulated in LUSC compared to LUAD. In conclusion, identified downstream networks revealed distinct biological mechanisms underlying cancer development and progression in LUSC and LUAD that may diversify the clinical outcome of the disease.
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http://dx.doi.org/10.1038/s41598-020-77284-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713208PMC
December 2020