scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

Prognostic Role of Estrogen Receptor Determination in Breast Cancer

1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recent Literature ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Role ◽  
Free Survival ◽  
The Difference ◽  
Disease Free ◽  
Actuarial Method

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.

scholarly journals H3K18Ac as a Marker of Cancer Progression and Potential Target of Anti-Cancer Therapy

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 485 ◽  
Author(s):  
Marta Hałasa ◽  
Anna Wawruszak ◽  
Alicja Przybyszewska ◽  
Anna Jaruga ◽  
Małgorzata Guz ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Posttranslational Modifications ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Future Perspectives ◽  
Free Survival ◽  
Histone 3 ◽  
Anti Cancer ◽  
Disease Free

Acetylation and deacetylation are posttranslational modifications (PTMs) which affect the regulation of chromatin structure and its remodeling. Acetylation of histone 3 at lysine placed on position 18 (H3K18Ac) plays an important role in driving progression of many types of cancer, including breast, colon, lung, hepatocellular, pancreatic, prostate, and thyroid cancer. The aim of this review is to analyze and discuss the newest findings regarding the role of H3K18Ac and acetylation of other histones in carcinogenesis. We summarize the level of H3K18Ac in different cancer cell lines and analyze its association with patients’ outcomes, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, we describe future perspectives of cancer therapeutic strategies based on H3K18 modifications.

scholarly journals Revising the Role of Integrin Subunit β4 Expression in Colon Cancer Progression and Survival: A Retrospective Study

2020 ◽  
Author(s):  
Eva Rademaker ◽  
Esther Bastiaannet ◽  
Jan Oosting ◽  
Neeltje G. Dekker-Ensink ◽  
Peter J. K. Kuppen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Integrin Subunit ◽  
Free Survival ◽  
Colon Cancer Progression ◽  
Level Versus ◽  
Disease Free

Abstract Background: Integrin subunit β4 (β4) has been proposed to play an important role in colon cancer progression through its involvement in hemidesmosome disassembly processes and tumor cell migration. However, no consensus has yet been achieved regarding its association with clinical outcomes, particularly in colon cancer. The aim of this study was to reveal the relation between β4 expression and clinicopathological features and colon cancer outcomes.Methods: Expression of β4 was assessed by immunohistochemistry in a large cohort of 651 colon cancer patients, the largest colon cancer cohort so far. Chi-square tests were used to study the association between β4 expression and clinicopathological features while its relation with disease-free survival was assessed by Cox proportional hazard models. Furthermore, a potential relation between levels of ITGB4 expression and patient outcomes was also investigated with the TCGA dataset.Results: No association between β4 expression and disease-free survival was encountered (P = 0.767), which disputes the role of β4 as a biomarker of malignant behavior in colon cancer. Strikingly, loss of β4 expression was instead associated with advanced pathological tumor (pT) stage of the primary tumor. Only 17.9% of the pT1 tumors displayed weak β4 expression level versus 28.1% of pT4 tumors, and 25.0% of the pT1 tumors had a high expression level versus 8.6% of the pT4 tumors (P = 0.012). Additionally, no relation was observed between β4 expression and colon cancer stage (P = 0.138), tumor differentiation grade (P = 0.097) or mismatch repair (MMR) status (P = 0.878).Conclusions: Contradictory reports have suggested opposite roles for β4 expression in (colon) cancer progression. In the present large cohort of colon cancer patients we found that β4 expression was not associated with worse clinical prognosis and tumor differentiation grade, but decreased with advanced pathological tumor stage. Future studies should establish whether loss of β4 expression promotes invasive characteristics of colon cancer cells.

scholarly journals Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

2020 ◽  
Vol 21 (13) ◽  
pp. 4687
Author(s):  
Nadia Ashour ◽  
Javier C. Angulo ◽  
Ana González-Corpas ◽  
María J. Orea ◽  
María V. T. Lobo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Epigenetic Silencing ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Prostate Cancer Progression ◽  
Free Survival ◽  
Disease Free

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.

scholarly journals Expression of Bcl-2 in Breast Cancer: Correlation with Clinicopathological Characteristics and Survival

2008 ◽  
Vol 51 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Filip Čečka ◽  
Helena Hornychová ◽  
Bohuslav Melichar ◽  
Aleš Ryška ◽  
Pavel Jandík ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Clinical Development ◽  
Free Survival ◽  
Broad Variety ◽  
Disease Free ◽  
Common Malignancy

Breast cancer is the most common malignancy in women. It is an immensely heterogeneous disease, characterised by a broad variety of clinical development. The research in recent years has focused on finding new markers of prognosis. This study investigates the role of expression of the bcl-2 protein in breast cancer. We analysed bcl-2 expression in 57 women with primary breast carcinoma who were treated with neoadjuvant (primary) chemotherapy, followed by a surgical procedure. The bcl-2 expression was correlated with other clinicopathological characteristics of the tumour – histological grade, stage, expression of hormonal receptors, proliferation rate, and with the survival of the patients. No significant association of bcl-2 expression with either overall survival or disease free survival was found.

scholarly journals TTK Predicts Triple Positive Breast Cancer Prognosis and Regulates Tumor Proliferation and Invasion

2021 ◽  
Author(s):  
Yunhe Gao ◽  
Shanshan Qu ◽  
Lanqing Cao ◽  
Min Yao
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Spindle Assembly Checkpoint ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free ◽  
Positive Breast Cancer

Abstract Background: This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. Methods: We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan–Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. Results: The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29–86 years). TTK expression was positively correlated with tumor size (P = 0.034), p53 status (P = 0.023), TNM stage (P = 0.023), and Ki-67 index (P< 0.001). The Kaplan–Meier curves revealed that TTK expression was correlated with poor disease-free survival (P = 0.001) and overall survival (P = 0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (P = 0.007 and P = 0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. Conclusions: The findings of the study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK may serve as a prognostic marker for TPBC.

Prognostic Role of C-Reactive Protein in Breast Cancer: A Systematic Review and Meta-Analysis

2011 ◽  
Vol 26 (4) ◽  
pp. 209-215 ◽  
Author(s):  
Yijie Han ◽  
Feng Mao ◽  
Ying Wu ◽  
Xiaonan Fu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
C Reactive Protein ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Disease Free

Background Recent studies have shown that C-reactive protein (CRP) may be associated with breast cancer. The purpose of this study is to summarize the predictive role of CRP for survival in breast cancer as shown in all available studies worldwide. Methods Related studies were identified and evaluated for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific, and disease-free survival (OS, CSS, and DFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP for survival were calculated. Results A total of 10 studies (n=4,502) were included for this meta-analysis (9 for OS, 3 for CSS, and 3 for DFS). For overall and disease-free survival, the pooled HRs of CRP were significant at 1.62 (95% confidence interval [95% CI], 1.20-2.18) and 1.81 (95% CI, 1.44-2.26), respectively. For cancer-specific survival, the pooled HR in higher CRP expression in breast cancer was 2.08 (95% CI, 1.48-2.94), which could strongly predict poorer survival in breast cancer. Conclusions CRP has a critical prognostic value in patients with breast cancer as an inflammation biomarker.

scholarly journals Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response

2021 ◽  
Vol 22 (6) ◽  
pp. 2826
Author(s):  
Viktor Hlaváč ◽  
Radka Václavíková ◽  
Veronika Brynychová ◽  
Pavel Ostašov ◽  
Renata Koževnikovová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variation ◽  
Cytochromes P450 ◽  
Disease Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Free Survival ◽  
Disease Free

Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 22 prioritized variants associating with a response or survival in the above evaluation phase were then analyzed by allelic discrimination in the large confirmation set (n = 802). Associations of variants in CYP1B1, CYP4F12, CYP4X1, and TBXAS1 with the response to the neoadjuvant cytotoxic chemotherapy were replicated by the confirmation phase. However, just association of variant rs17102977 in CYP4X1 passed the correction for multiple testing and can be considered clinically and statistically validated. Replicated associations for variants in CYP4X1, CYP24A1, and CYP26B1 with disease-free survival of all patients or patients stratified to subgroups according to therapy type have not passed a false discovery rate test. Although statistically not confirmed by the present study, the role of CYP genes in breast cancer prognosis should not be ruled out. In conclusion, the present study brings replicated association of variant rs17102977 in CYP4X1 with the response of patients to the neoadjuvant cytotoxic chemotherapy and warrants further research of genetic variation CYPs in breast cancer.

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