scholarly journals A Prognostic Model for Breast Cancer Based on Cancer Incidence-Related DNA Methylation Pattern

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhenchong Xiong ◽  
Lin Yang ◽  
Juan Ao ◽  
Jiarong Yi ◽  
Xiazi Zouxu ◽  
...  

Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer-related deaths in women. The purpose of this study was to develop a prognostic model based on BC-related DNA methylation pattern. A total of 361 BC incidence-related probes (BCIPs) were differentially methylated in blood samples from women at high risk of BC and BC tissues. Twenty-nine of the 361 BCIPs that significantly correlated with BC outcomes were selected to establish the BCIP score. BCIP scores based on BC-related DNA methylation pattern were developed to evaluate the mortality risk of BC. The correlation between overall survival and BCIP scores was assessed using Kaplan–Meier, univariate, and multivariate analyses. In BC, the BCIP score was significantly correlated with malignant BC characteristics and poor outcomes. Furthermore, we assessed the BCIP score-related gene expression profile and observed that genes with expressions associated with the BCIP score were involved in the process of cancer immunity according to GO and KEGG analyses. Using the ESTIMATE and CIBERSORT algorithms, we discovered that BCIP scores were negatively correlated with both T cell infiltration and immune checkpoint inhibitor response markers in BC tissues. Finally, a nomogram comprising the BCIP score and BC prognostic factors was used to establish a prognostic model for patients with BC, while C-index and calibration curves were used to evaluate the effectiveness of the nomogram. A nomogram comprising the BCIP score, tumor size, lymph node status, and molecular subtype was developed to quantify the survival probability of patients with BC. Collectively, our study developed the BCIP score, which correlated with poor outcomes in BC, to portray the variation in DNA methylation pattern related to BC incidence.

2015 ◽  
Vol 4 (2) ◽  
pp. 120
Author(s):  
AliM Ardekani ◽  
Hamed Abdolghafoorian ◽  
Arootin Gharibiyan ◽  
SeyedAhmad Hashemi ◽  
Mahdie Hadi

Epigenetics ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. 300-306 ◽  
Author(s):  
Breezy Malakkaran Lindqvist ◽  
Sanja A. Farkas ◽  
Sten Wingren ◽  
Torbjörn K. Nilsson

2012 ◽  
Vol 135 (3) ◽  
pp. 705-713 ◽  
Author(s):  
Sandeep Kumar Botla ◽  
Amin Moghaddas Gholami ◽  
Mahdi Malekpour ◽  
Evgeny A. Moskalev ◽  
Mahdi Fallah ◽  
...  

2015 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
AliM Ardekani ◽  
Arootin Gharibiyan ◽  
SeyedAhmad Hashemi ◽  
Mahdie Hadi ◽  
Hamed Abdolghafoorian

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 332
Author(s):  
Krystyna Fabianowska-Majewska ◽  
Agnieszka Kaufman-Szymczyk ◽  
Aldona Szymanska-Kolba ◽  
Jagoda Jakubik ◽  
Grzegorz Majewski ◽  
...  

One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.


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