scholarly journals ACSL3 As a Potential Prognostic Biomarker in Patients With Breast Cancer

Author(s):  
Xiangyu Sun ◽  
Meng Li ◽  
Mozhi Wang ◽  
Mengshen Wang ◽  
Haoran Dong ◽  
...  

Abstract Objective: To explore the expression pattern of long chain fatty acyl CoA synthetase 3 (ACSL3) in breast cancer, and evaluate the clinical significance of ACSL3 by analyzing potential function and prognostic value of ACSL3 in human breast carcinoma.Methods: The expression of ACSL3 in normal mammary tissues and breast tumor tissues was analyzed by GEPIA and Human Protein Atlas. The prognostic value of ACSL3 was evaluated by Kaplan–Meier plotter analysis. ACSL3 expression was analyzed by immunohistochemistry in 297 breast cancer patients from the First Hospital of China Medical University Furthermore, based on LinkedOmics database, analyses of GO and KEGG pathways were performed to identify the potential function of ACSL3. Tumor Immune Estimation Resource (TIMER) database was used to evaluate the association between ACSL3 and immune infiltration in breast cancer. Results: GEPIA and Human Protein Atlas indicated that ACSL3 was significantly upregulated in breast carcinomas. Kaplan-Meier plotter analysis showed that increased expression of ACSL3 mRNA was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) in breast cancer patients. Results from immunochemical staining showed that ACSL3 was obviously related to clinicopathological features of breast cancer, and ACSL3 was highly abundant in TNBC tumors. Moreover, survival analysis of breast cancer patients demonstrated that higher ACSL3 protein expression is unfavorable prognostic biomarker in breast cancer patients. Results from TIMER database indicated that ACSL3 expression was significantly correlated with infiltration level of multiple immune cells. Further studies are needed to explore underlying mechanism of the pro-tumor effects of ACSL3 expression.Conclusions: ACSL3 may not only serve as a reliable predictive biomarker of breast cancer but also have impact on the occurrence and progression of breast cancer. Thus, ACSL3 may be an emerging therapeutic target for the development of molecular-targeted therapeutic strategies for breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Xianghou Xia ◽  
Wenjuan Yin ◽  
Jiefei Mao ◽  
Jiejie Hu ◽  
Dehong Zou ◽  
...  

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.


2020 ◽  
Vol 11 ◽  
Author(s):  
Bo Zhang ◽  
Yanlin Gu ◽  
Guoqin Jiang

PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and MethodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 246
Author(s):  
Daiana L. Vitale ◽  
Ilaria Caon ◽  
Arianna Parnigoni ◽  
Ina Sevic ◽  
Fiorella M. Spinelli ◽  
...  

UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.


2020 ◽  
Author(s):  
Jia-Xiang An ◽  
Ying-Ying Chen ◽  
Zhao-Sheng Ma ◽  
Wen-Jie Yu ◽  
Jin-Xi Hu ◽  
...  

Abstract Background: CXCL2 is a part of chemokine superfamily, which encodes secretory proteins involved in immune regulation and inflammation. The correlation between CXCL2 and prognosis of different cancers, tumor infiltrating lymphocytes are not clear. Methods: We analyzed the expression of CXCL2 and its effect on clinical prognosis through Oncomine database, Tumor Immune Estimation Resource (TIMER) website, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA were used to analyze the correlation between CXCL2 and the gene marker of immune infiltration. StarBase was used to predict the miRNA that may regulate CXCL2. The relationship between miR-532-5p and CXCL2 was detected by qRT-PCR. Kaplan-Meier plotter was used to evaluate the impact of miR-532-5p on clinical prognosis. Results: PrognoScan, Kaplan-Meier plotter and GEPIA database analysis showed that low expression of CXCL2 was associated with poor disease-specific survival time (DSS), relapse-free survival time (RFS) and overall disease survival (OS) in breast cancer patients. In addition, low expression of CXCL2 was associated with poor OS and RFS in patients with lymph node positive breast cancer. CXCL2 expression was positively correlated with the infiltration of B cells, CD4+T and CD8+T cells, neutrophils and dendritic cells (DCs) in BRCA, mainly in Luminal breast cancer. MiR-532-5p can directly regulate CXCL2 expression. High miR-532-5p expression is significantly correlated with HER2 negative, grade 2 and 3 and poor OS in patients with HER+ER- breast cancer. Conclusion: CXCL2 is closely related to the prognosis and immune infiltration level of breast cancer patients, it can be regulated by miR-532-5p.


2011 ◽  
Vol 47 ◽  
pp. S333
Author(s):  
M. Riaz ◽  
A. Sieuwerts ◽  
M. Look ◽  
M. Smid ◽  
J. Foekens ◽  
...  

2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.


2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values&gt;0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.


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