DNA methylation and breast cancer: A way forward (Review)

Vietri, Maria Teresa; Goletti, Delia; Benincasa, Giuditta; Ferraro, Giuseppe; Caliendo, Gemma; Nicoletti, Giovanni Francesco; Napoli, Claudio

doi:10.3892/ijo.2021.5278

Cited by 25 publications

(12 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another mechanism of TAM-mediated cancer progression worth noting is via the methylation of breast cancer-specific genes to regulate gene expression [96]. A recent paper discovered that TAMs secrete IL-6 in the TME to stimulate protein arginine methyltransferase 1 (PRMT1)-mediated meR342-EZH2 formation in order to stabilize the enhancer of Zeste Homolog 2 (EZH2) in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

View full text Add to dashboard Cite

The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Gene expression is strongly influenced by DNA methylation, an epigenetic modification associated with transcriptional silencing. Tumor suppressor genes (e.g., BRCA1, ATM) are often hypermethylated in patient tumors and in peripheral blood [109,110]. Targeted and genome-wide DNA methylation studies have identified specific methylation changes associated with increased breast cancer risk and BC prognosis [111].…”

Section: Peripheral Blood Cell Transcriptome and Therapy Response And...mentioning

confidence: 99%

“…Treatment with chemotherapeutics or immunotherapy was shown to cause acquired methylation-associated resistance in cell models, and therapy resistance was also observed in BC patients [114,115]. The use of epigenetic drugs (e.g., DNMT inhibitors) is being tested in combination with chemotherapy, immunotherapy, and other treatments to overcome epigenetic alterations and treatment resistance (Figure 2) [109,116].…”

Section: Peripheral Blood Cell Transcriptome and Therapy Response And...mentioning

confidence: 99%

Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

Čelešnik

Potočnik

2022

Cancers

View full text Add to dashboard Cite

Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.

show abstract

“…Pancreatic cancer arises in several hereditary syndromes, including Hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li–Fraumeni syndrome (LFS), Peutz–Jeghers syndrome (PJS), and Hereditary pancreatitis (HP) [ 5 , 6 , 7 , 8 ]. Most familial pancreatic cancer (FPC) is attributable to HBOC syndrome that results from germline mutations in BRCA1/2 genes and other genes such as ATM, BRIP1, CHEK2, RAD50 , and RAD51C [ 9 , 10 ]. In FPC belonging to HBOC, BRCA2 mutations are the most common genetic alteration, observed in about 5–10% of cases [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Vietri

Goletti

Caliendo

et al. 2022

Genes

Self Cite

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer death worldwide; most of cases are sporadic, however about 5% to 10% report a hereditary predisposition. Several hereditary syndromes have been associated with familial pancreatic cancer (FPC) onset, including hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li–Fraumeni syndrome (LFS),Peutz–Jeghers syndrome (PJS), and Hereditary pancreatitis (HP).The aim of this study was to determine the mutational status of a cohort of 56 HBOC families, 7 LS families, 3 FAP and FAMMM families, and 1 LFS family with at least one case of PDAC. Mutation analysis of BRCA1/2, ATM, CHEK2, PALB2, RAD51C, RAD51D, NBN, CDH1, TP53, MLH1, MSH2, MSH6, and PMS2genes, showedmutation in BRCA1/2, MLH1, and APC genes. We founda high mutation rate in patients belong HBOC and LS families, with a percentage of 28.6% in both syndromes and prevalence in HBOC of BRCA2 mutations with one case of double mutation in BRCA2 gene. In FAP family, we found a pathogenic mutation in APC gene in 1/3 families. We observed an early onset of PDAC and a lower survival in PDAC patients belonging to mutated families, while no evidence of possible pancreatic cancer cluster regions was found. Moreover, we identified a novel BRCA2 germline mutation, c.5511delT (p.Phe1837LeufsX3), not reported in any database, that segregated with disease in HBOC patients. Mutational analysis was extended to family membersof mutated patients, both healthy and cancer affected, which revealed 23 unaffected family members that inherited the proband’s mutation. Although correlative by its nature, the presence of a BRCA mutation in PDAC patients may have benefits in terms of optimized treatment and longer outcome.

show abstract

DNA methylation and breast cancer: A way forward (Review)

Cited by 25 publications

References 84 publications

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Contact Info

Product

Resources

About