High FAS expression correlates with a better prognosis and efficacy of taxanes and target regents in breast cancer

2021 ◽  
pp. 1-13
Author(s):  
Yi Zhang ◽  
Xuan Shao ◽  
Chenyi Gao ◽  
Danying Xu ◽  
Jun Wu ◽  
...  

BACKGROUND: FAS can serve as both an oncogene and a suppresser in different malignancies, and the prognostic value of FAS remains controversial. METHODS: The Oncomine database, KM-Plotter and bc-GenExMiner platform were adopted to analyze the prognostic value of FAS in breast cancer. Breast cancer tissue microarrays were further used to verify these data. The Cell Miner Tool was used to predict the value of FAS mRNA expression in predicting the efficacies of clinical drugs. RESULTS: We found that both FAS mRNA and protein expression level significantly reduced in breast carcinoma. In addition, high FAS expression indicates a better metastatic relapse-free survival. Interestingly, FAS was associated with a better prognosis in different subtypes of breast cancer patients, namely, only in grade II and III, lymph nodal positive or p53 wild-type patients. The data from the Cell Miner Tool revealed that FAS mRNA expression was correlated with the efficacy of the first-line chemotherapeutic taxane agents and target drugs including olaparib and everolimus. CONCLUSIONS: FAS expression correlates with a better prognosis in breast cancer and may provide an effective clinical strategy to predict the sensitivity of taxanes and targeted drugs.

2020 ◽  
Vol 9 (10) ◽  
pp. 3153
Author(s):  
Pei-Yi Chu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
En-Pei Isabel Chiang

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.


2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Weiwei Gong ◽  
Yueyang Liu ◽  
Sarah Preis ◽  
Xiaocong Geng ◽  
Agnes Petit-Courty ◽  
...  

2018 ◽  
Vol 7 (10) ◽  
pp. 5066-5082 ◽  
Author(s):  
Marinos Tsiatas ◽  
Konstantine T. Kalogeras ◽  
Kyriaki Manousou ◽  
Ralph M. Wirtz ◽  
Helen Gogas ◽  
...  

2009 ◽  
Vol 75 (9) ◽  
pp. 769-775 ◽  
Author(s):  
Sabina Siddiqui ◽  
C. Todd Bruker ◽  
Daniel P. Kestler ◽  
James S. Foster ◽  
Keith D. Gray ◽  
...  

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using χ2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage ( P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy ( P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II ( P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV ( P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage ( P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.


2020 ◽  
Vol 21 (15) ◽  
pp. 5453
Author(s):  
Noha Mitwally ◽  
Einas Yousef ◽  
Ahmad Abd Al Aziz ◽  
Mohamed Taha

Phospholipase A2 receptor 1 (PLA2R1) expression and its role in the initiation and progression of breast cancer are an unresolved issue. PLA2R1 was found to endorse several tumor suppressive responses, including cellular senescence and apoptosis. Previous in vitro studies demonstrated that DNA hypermethylation was highly associated with the epigenetic silencing of PLA2R1 in breast cancer cell lines. Our objective was to study the level of PLA2R1 mRNA expression and the methylation of its promoter in different histological grades and molecular subtypes of breast cancer. We performed bioinformatics analyses on available human breast cancer expression datasets to assess the PLA2R1 mRNA expression. We used qRT-PCR to evaluate the PLA2R1 mRNA expression and its promoter’s methylation in breast cancer tissue in comparison to breast fibroadenomas. Our results describe, for the first time, the expression of PLA2R1 and the methylation of its promoter in human breast cancer tissues. A significant downregulation of PLA2R1, together with hypermethylation of the promoter was detected in breast cancers of different histological grades and molecular subtypes when compared to benign breast tissues. PLA2R1 promoter hypermethylation was associated with aggressive subtypes of breast cancer. In conclusion, PLA2R1 promoter hypermethylation is a potentially useful diagnostic and prognostic biomarker and could serve as a possible therapeutic target in breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2431
Author(s):  
Lukas Lenga ◽  
Simon Bernatz ◽  
Simon S. Martin ◽  
Christian Booz ◽  
Christine Solbach ◽  
...  

Dual-energy CT (DECT) iodine maps enable quantification of iodine concentrations as a marker for tissue vascularization. We investigated whether iodine map radiomic features derived from staging DECT enable prediction of breast cancer metastatic status, and whether textural differences exist between primary breast cancers and metastases. Seventy-seven treatment-naïve patients with biopsy-proven breast cancers were included retrospectively (41 non-metastatic, 36 metastatic). Radiomic features including first-, second-, and higher-order metrics as well as shape descriptors were extracted from volumes of interest on iodine maps. Following principal component analysis, a multilayer perceptron artificial neural network (MLP-NN) was used for classification (70% of cases for training, 30% validation). Histopathology served as reference standard. MLP-NN predicted metastatic status with AUCs of up to 0.94, and accuracies of up to 92.6 in the training and 82.6 in the validation datasets. The separation of primary tumor and metastatic tissue yielded AUCs of up to 0.87, with accuracies of up to 82.8 in the training, and 85.7 in the validation dataset. DECT iodine map-based radiomic signatures may therefore predict metastatic status in breast cancer patients. In addition, microstructural differences between primary and metastatic breast cancer tissue may be reflected by differences in DECT radiomic features.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.


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