scholarly journals Data mining analysis of miR-638 and key genes interaction in cisplatin resistant triple-negative breast cancer

2019 ◽  
Vol 24 (2) ◽  
pp. 65
Author(s):  
Adam Hermawan ◽  
Herwandhani Putri
Keyword(s):  
Breast Cancer ◽  
Regulatory Networks ◽  
Target Gene ◽  
Resistance Mechanism ◽  
Mrna Levels ◽  
Kaplan Meier ◽  
Gene Regulatory ◽  
Survival Plot ◽  
Geo Database

Cisplatn is one of the chemotherapy for the treatment of triple‐negatve breast cancer (TNBC), but its effectveness is limited because of the phenomenon of chemoresistance. miR‐638 was shown to regulate chemoresistance; however, it has never been validated in the cisplatn‐resistant tumor from patents. This present study aimed to identfy the key gene regulatory networks of miR‐638 and evaluate the potental role of the miR‐638 and its targets as potental prognosis biomarkers for cisplatn‐resistance triple‐negatve breast cancer patents. The miR‐638 target was obtained from the miRecords database while the mRNA of chemoresistance biomarker candidate was obtained from the GSE18864 of GEO database, which is mRNA of cisplatn‐resistance TNBC patents. CCND1 and FZD7 are potental candidates for cisplatn chemoresistance biomarkers in patents with TNBC. Moreover, a Kaplan‐Meier survival plot showed that breast cancer patents with low mRNA levels of FZD7 had signifcantly worse overall survival than those in higher mRNA expression group. Taken together, miR‐638 plays a role in cisplatn resistance mechanism through a mechanism involving its target gene CCND1 and FZD7. Overall, miR‐638, CCND1, and FZD7 are candidates for cisplatn biomarker resistance in TNBC.

scholarly journals Molecular characterization of ageratum enation virus and beta satellite associated with leaf curl disease of fenugreek in India

2019 ◽  
Vol 24 (2) ◽  
pp. 74
Author(s):  
P Swarnalatha ◽  
V Venkataravanappa ◽  
C N Lakshminarayana Reddy ◽  
M Sunil Kumar ◽  
M Krishna Reddy
Keyword(s):  
Breast Cancer ◽  
Regulatory Networks ◽  
Resistance Mechanism ◽  
Mrna Levels ◽  
Kaplan Meier ◽  
Survival Plot ◽  
Leaf Curl Disease ◽  
Geo Database

Cisplatn is one of the chemotherapy for the treatment of triple‐negatve breast cancer (TNBC), but its effectveness is limited because of the phenomenon of chemoresistance. miR‐638 was shown to regulate chemoresistance; however, it has never been validated in the cisplatn‐resistant tumor from patents. This present study aimed to identfy the key gene regulatory networks of miR‐638 and evaluate the potental role of the miR‐638 and its targets as potental prognosis biomarkers for cisplatn‐resistance triple‐negatve breast cancer patents. The miR‐638 target was obtained from the miRecords database while the mRNA of chemoresistance biomarker candidate was obtained from the GSE18864 of GEO database, which is mRNA of cisplatn‐resistance TNBC patents. CCND1 and FZD7 are potental candidates for cisplatn chemoresistance biomarkers in patents with TNBC. Moreover, a Kaplan‐Meier survival plot showed that breast cancer patents with low mRNA levels of FZD7 had signifcantly worse overall survival than those in higher mRNA expression group. Taken together, miR‐638 plays a role in cisplatn resistance mechanism through a mechanism involving its target gene CCND1 and FZD7. Overall, miR‐638, CCND1, and FZD7 are candidates for cisplatn biomarker resistance in TNBC.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

scholarly journals KBoost: a new method to infer gene regulatory networks from gene expression data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luis F. Iglesias-Martinez ◽  
Barbara De Kegel ◽  
Walter Kolch
Keyword(s):  
Breast Cancer ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Bayesian Model Averaging ◽  
Model Averaging ◽  
R Package ◽  
Breast Cancer Patients ◽  
Sources Of Information ◽  
Cancer Subtypes ◽  
Gene Regulatory

AbstractReconstructing gene regulatory networks is crucial to understand biological processes and holds potential for developing personalized treatment. Yet, it is still an open problem as state-of-the-art algorithms are often not able to process large amounts of data within reasonable time. Furthermore, many of the existing methods predict numerous false positives and have limited capabilities to integrate other sources of information, such as previously known interactions. Here we introduce KBoost, an algorithm that uses kernel PCA regression, boosting and Bayesian model averaging for fast and accurate reconstruction of gene regulatory networks. We have benchmarked KBoost against other high performing algorithms using three different datasets. The results show that our method compares favorably to other methods across datasets. We have also applied KBoost to a large cohort of close to 2000 breast cancer patients and 24,000 genes in less than 2 h on standard hardware. Our results show that molecularly defined breast cancer subtypes also feature differences in their GRNs. An implementation of KBoost in the form of an R package is available at: https://github.com/Luisiglm/KBoost and as a Bioconductor software package.

scholarly journals The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4576
Author(s):  
Hung-Yu Lin ◽  
Hui-Wen Ho ◽  
Yen-Hsiang Chang ◽  
Chun-Jui Wei ◽  
Pei-Yi Chu
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Drug Resistant ◽  
Therapeutic Targeting ◽  
The Past ◽  
Regulated Cell Death ◽  
Common Malignancy

Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.

scholarly journals Prognostic role of GPER/Ezrin in triple-negative breast cancer is associated with menopausal status

2019 ◽  
Vol 8 (6) ◽  
pp. 661-671 ◽  
Author(s):  
Shuang Ye ◽  
Yuanyuan Xu ◽  
Jiehao Li ◽  
Shuhui Zheng ◽  
Peng Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Menopausal Status ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Survival Prognosis ◽  
Kaplan Meier

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

scholarly journals Evolution of gene regulatory networks by means of selection and random genetic drift

2018 ◽  
Author(s):  
Antonios Kioukis ◽  
Pavlos Pavlidis
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Genetic Drift ◽  
Regulatory Networks ◽  
Fitness Landscape ◽  
Random Genetic Drift ◽  
Maturation Period ◽  
Evolutionary Forces ◽  
Gene Regulatory

The evolution of a population by means of genetic drift and natural selection operating on a gene regulatory network (GRN) of an individual has not been scrutinized in depth. Thus, the relative importance of various evolutionary forces and processes on shaping genetic variability in GRNs is understudied. Furthermore, it is not known if existing tools that identify recent and strong positive selection from genomic sequences, in simple models of evolution, can detect recent positive selection when it operates on GRNs. Here, we propose a simulation framework, called EvoNET, that simulates forward-in-time the evolution of GRNs in a population. Since the population size is finite, random genetic drift is explicitly applied. The fitness of a mutation is not constant, but we evaluate the fitness of each individual by measuring its genetic distance from an optimal genotype. Mutations and recombination may take place from generation to generation, modifying the genotypic composition of the population. Each individual goes through a maturation period, where its GRN reaches equilibrium. At the next step, individuals compete to produce the next generation. As time progresses, the beneficial genotypes push the population higher in the fitness landscape. We examine properties of the GRN evolution such as robustness against the deleterious effect of mutations and the role of genetic drift. We confirm classical results from Andreas Wagner’s work that GRNs show robustness against mutations and we provide new results regarding the interplay between random genetic drift and natural selection.

MCRS1 EXPRESSION MORE IN TUMOR PART AND SERVES AS A POOR PROGNOSTIC FACTOR IN EXTRAHEPATIC CHOLANGIOCARCINOMA

2021 ◽  
pp. 72-75
Author(s):  
Hung-Chune Maa ◽  
Pham van Tuyen ◽  
Yen-Lin Chen ◽  
Yao-Nan Yuan
Keyword(s):  
Prognostic Factor ◽  
Large Scale ◽  
Surgical Margin ◽  
P Value ◽  
Extrahepatic Cholangiocarcinoma ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Survival Plot

INTRODUCTION:Microporous protein 1 (MCRS1) acts as a cancer gene. MCRS1 is associated with poor prognosis in several types of cancer including colorectal cancer, hepatocellular carcinoma, glioma, and non-small cell lung cancer. In the current study, we are trying to shed light on the role of MCRS1 in the extrahepatic cholangiocarcinoma. METHODS: We retrospectively selected 13 patients who diagnosed extrahepatic cholangiocarcinoma. All clinical charts and histopathology reports were reviewed for and recoded for age, gender, tumor size, surgical margin status, lymph node metastasis, distant metastasis and TMN staging. All patients were followed for 1~10 years. The median follow-up period was 3.2 years. RESULTS: The expression level of MCRS1 showed signicantly higher in tumor part than non-tumor part. In the Kaplan-Meier survival plot , the high MCRS1 expression group showed poor survival probability with p value of 0.020. The Hazard ratio of MCRS1 showed 8.393 folds in high MCRS1 expression group when compared with low expression group with the borderline p value of 0.05. CONCLUSION:MCRS1 serves as a poor prognostic factor. Further analysis, no correlation was found in proliferation, apoptosis, angiogenesis and EMT markers. The reason may be the sample size and large-scale study in the future is mandatory

Effect of mast cells on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11522-11522
Author(s):  
Mark Wroblewski ◽  
Janna-Lisa Velthaus ◽  
Raimund Bauer ◽  
Volkmar Müller ◽  
Christian Schem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Granzyme B ◽  
Resistance Mechanism ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Kaplan Meier

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.

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