scholarly journals Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

2020 ◽  
Author(s):  
Yier Qiu ◽  
Guowen Lu ◽  
Yingjie Wu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Mrna Expression ◽  
Protective Factor ◽  
Killer Cell ◽  
Cytokine Receptor ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Receptor Interactions ◽  
Cancer Tissues

Abstract Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.Conclusion: Our research demonstrated that high CDKN2A mRNA expression may be an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

scholarly journals Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

2020 ◽  
Author(s):  
Yier Qiu ◽  
Guowen Lu ◽  
Yingjie Wu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Mrna Expression ◽  
Protective Factor ◽  
Killer Cell ◽  
Cytokine Receptor ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Receptor Interactions ◽  
Cancer Tissues

Abstract Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.Conclusion: Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

scholarly journals Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

2020 ◽  
Author(s):  
Yier Qiu ◽  
Guowen Lu ◽  
Yingjie Wu
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Mrna Expression ◽  
Protective Factor ◽  
Killer Cell ◽  
Cytokine Receptor ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Receptor Interactions ◽  
Cancer Tissues

Abstract Background Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer. Method Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set. Results We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group. Conclusion Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

scholarly journals Bioinformatic analysis reveals GSG2 as a potential target for breast cancer therapy

2019 ◽  
Vol 14 (1) ◽  
pp. 688-698
Author(s):  
Zheng Ye ◽  
Zhaoyu Zhang ◽  
Lijiao Fang ◽  
Daiquan Tian ◽  
Xin Liu
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Copy Number ◽  
Bioinformatic Analysis ◽  
Copy Number Variations ◽  
Breast Cancer Therapy ◽  
Normal Tissues ◽  
Cancer Tissues

AbstractObjectiveTo explore the potential role of GSG2 in breast cancer progression.MethodsThe mRNA expression, DNA copy number and clinical data used in this study were obtained from the TCGA data portal. The copy number variations (CNVs) thresholds were determined according to the set of discrete copy number calls provided by Genomic Identification of Significant Targets in Cancer (GISTIC).ResultsThe mRNA expression level of GSG2 in 112 breast cancer tissues was much higher than that in adjacent normal tissues. GSG2 was significantly upregulated in stage II compared with stage I, and there was no differential expression of GSG2 between tumors with or without metastasis. Heterozygous deletion occupied 57.1% of CNVs for GSG2 gene in breast cancer samples. Patients with higher GSG2 expression tended to suffer from poorer prognosis.ConclusionOur profiling analysis indicated the overexpression of GSG2 might play an important role in breast cancer development, suggesting that GSG2 could be a new target for breast cancer treatment, making GSG2 inhibitors becoming potential drugs for breast cancer therapy.

scholarly journals Integrative Bioinformatics Study of Tangeretin Potential Targets for Preventing Metastatic Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Adam Hermawan ◽  
Herwandhani Putri ◽  
Naufa Hanif ◽  
Muthi Ikawati
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Genetic Alterations ◽  
Pathway Enrichment ◽  
Normal Tissues ◽  
Kaplan Meier

Agents that target metastasis are important to improve treatment efficacy in patients with breast cancer. Tangeretin, a citrus flavonoid, exhibits antimetastatic effects on breast cancer cells, but its molecular mechanism remains unclear. Tangeretin targets were retrieved from PubChem, whereas metastatic breast cancer regulatory genes were downloaded from PubMed. In total, 58 genes were identified as potential therapeutic target genes of tangeretin (PTs). GO and KEGG pathway enrichment analyses of PTs were performed using WebGestalt (WEB-based Gene SeT AnaLysis Toolkit). The PPI network was analyzed using STRING-DB v11.0 and visualized by Cytoscape software. Hub genes were selected on the basis of the highest degree score as calculated by the CytoHubba plugin. Genetic alterations of the PTs were analyzed using cBioPortal. The prognostic values of the PTs were evaluated with the Kaplan–Meier plot. The expression of PTs across breast cancer samples was confirmed using GEPIA. The reliability of the PTs in metastatic breast cancer cells was validated using ONCOMINE. Molecular docking was performed to foresee the binding sites of tangeretin with PIK3Cα, MMP9, PTGS2, COX-2, and IKK. GO analysis showed that PTs participate in the biological process of stimulus response, are the cellular components of the nucleus and the membrane, and play molecular roles in enzyme regulation. KEGG pathway enrichment analysis revealed that PTs regulate the PI3K/Akt pathway. Genetic alterations for each target gene were MTOR (3%), NOTCH1 (4%), TP53 (42%), MMP9 (4%), NFKB1 (3%), PIK3CA (32%), PTGS2 (15%), and RELA (5%). The Kaplan–Meier plot showed that patients with low mRNA expression levels of MTOR, TP53, MMP9, NFKB1, PTGS2, and RELA and high expression of PIK3CA had a significantly better prognosis than their counterparts. Further validation of gene expression by using GEPIA revealed that the mRNA expression of MMP9 was significantly higher in breast cancer tissues than in normal tissues, whereas the mRNA expression of PTGS2 showed the opposite. Analysis with ONCOMINE demonstrated that the mRNA expression levels of MMP9 and NFKB1 were significantly higher in metastatic breast cancer cells than in normal tissues. The results of molecular docking analyses revealed the advantage of tangeretin as an inhibitor of PIK3CA, MMP9, PTGS2, and IKK. Tangeretin inhibits metastasis in breast cancer cells by targeting TP53, PTGS2, MMP9, and PIK3CA and regulating the PI3K/Akt signaling pathway. Further investigation is needed to validate the results of this study.

scholarly journals Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Prognostic Value ◽  
Diagnostic Value ◽  
Roc Curve Analysis ◽  
Free Survival ◽  
Flap Endonuclease 1 ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

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>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.

The glycobiological landscape of breast cancer: insights into galectins and O-GlcNAc homeostasis-related genes

2021 ◽  
Author(s):  
Rada Tazhitdinova ◽  
Alexander V Timoshenko
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Breast Cancer Subtype ◽  
The Cancer Genome Atlas ◽  
Correlation Relationship ◽  
Cancer Data ◽  
Normal Tissues ◽  
Genes Encoding ◽  
Genetic Landscape ◽  
Cancer Tissues

Abstract Purpose This study aimed to assess the functional associations between genes of the glycobiological landscape encoding galectins and O-GlcNAc cycle enzymes in the context of breast cancer biology and clinical applications. Methods An in silico analysis of the breast cancer data from The Cancer Genome Atlas was conducted comparing expression, pairwise correlations, and prognostic value for 17 genes encoding galectins, O-GlcNAc cycle enzymes, and cell stemness-related transcription factors. Results Multiple general and breast cancer subtype-specific differences in galectin/O-GlcNAc genetic landscape markers were observed and classified. Specifically, LGALS12 was found to be significantly downregulated in breast cancer tissues across all subtypes while LGALS2 and GFPT1 showed potential as prognostic markers. Remarkably, there was an overall loss of both correlation strength and correlation relationship between expression of galectin/O-GlcNAc landscape genes in the breast cancer samples versus normal tissues. Six gene pairs (GFPT1/LGALS1, GFPT1/LGALS3, GFPT1/LGALS12, GFPT1/KLF4, OGT/LGALS12, and OGT/KLF4) were found to be potential diagnostic markers for breast cancer. Conclusions These findings indicate that the glycobiological landscape of breast cancer underwent significant remodeling, which might be associated with switching galectin gene regulation within a framework of O-GlcNAc homeostasis.

PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng
Keyword(s):  
Bladder Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Histological Grade ◽  
Tnm Stage ◽  
Cox Regression Analysis ◽  
Relative Expression ◽  
Kaplan Meier ◽  
Normal Bladder ◽  
Cancer Tissues

Abstract Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.

scholarly journals PAQR6 expression enhancement suggests a worse prognosis in prostate cancer patients

2018 ◽  
Vol 13 (1) ◽  
pp. 511-517 ◽  
Author(s):  
Bin Li ◽  
Zhe Lin ◽  
Quan Liang ◽  
Yuan Hu ◽  
Wen-Feng Xu
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Survival Rates ◽  
Mapk Signaling ◽  
Du145 Cell ◽  
Kaplan Meier ◽  
Prostate Cancer Development ◽  
And Migration ◽  
Cancer Tissues

AbstractObjectiveThis study aimed to evaluate the expression of progestin and adipoQ receptor family member VI (PAQR6, mPRδ) in prostate cancer and to explore its role in prostate cancer progression.MethodsPAQR6 mRNA expression was evaluated based on the data obtained from the TCGA database and the GEO database. The prognostic value of PAQR6 was explored by Kaplan-Meier analysis. To investigate the role of PAQR6, it was depleted by siRNA in DU145 cells. The effects of depleting PAQR6 on DU145 cell viability and migration were determined by CCK8 assay, colony formation assay, and wound healing assay, respectively. The activation of MEK and ERK were analyzed by western blot.ResultsPAQR6 mRNA expression was significantly up-regulated in prostate cancer tissues and correlated with lower survival rates (p=0.014). Furthermore, qPCR revealed that PAQR6 expression was elevated in DU145 and LNCaP cells compared with RWPE-2 cells. Depleting PAQR6 obviously suppressed DU145 cell proliferation and migration (p<0.01). In addition, the ratio of p-MEK/MEK and p-ERK/ERK was significantly reduced after silencing PAQR6 (p<0.01).ConclusionPAQR6 might play a facilitating role in prostate cancer development by regulating the MAPK signaling pathway. Moreover, it might serve as a potential predictor and therapeutic target in prostate cancer.

scholarly journals The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Rui-min Ma ◽  
Fan Yang ◽  
Du-ping Huang ◽  
Min Zheng ◽  
Yi-luan Wang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Mrna Level ◽  
The Cancer Genome Atlas ◽  
Paired Samples ◽  
Cancer Genome Atlas ◽  
Advanced Stages ◽  
Independent Risk Factors ◽  
Cancer Tissues ◽  
Structural Maintenance Of Chromosomes

Aim. To investigate the mRNA expression and clinical significance of structural maintenance of chromosomes protein 4 (SMC4) in breast cancer. Methods. A total of 23 paired samples were sequenced, and data from the Cancer Genome Atlas were analyzed. Results. SMC4 mRNA level was significantly upregulated in breast cancer tissues (P<0.001). Patients with high mRNA expression of SMC4 had significantly poor survival (P=0.012). Subgroup analyses show that in nontriple negative breast cancer (non-TNBC) patients, the high SMC4 mRNA expression, older age (>65), negative progesterone receptor, and advanced stages (III-IV) were independent risk factors (HR=3.293, 95% CI 1.257-8.625, P=0.015). In patients with TNBC, high mRNA expression of SMC4 correlated with better survival rate (P<0.046). Conclusion. SMC4 mRNA level is a good prognostic biomarker for patients with breast cancer.

Utility of a multigene prognostic algorithm in combination with TP53 expression for prediction of benefit from adjuvant taxane-containing chemotherapy in node-positive breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 593-593
Author(s):  
R. Kronenwett ◽  
U. Stropp ◽  
E. Briasoulis ◽  
M. Gehrmann ◽  
E. Razis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Prognostic Score ◽  
Phase Iii ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Tissue Samples ◽  
Node Positive ◽  
Kaplan Meier ◽  
Formalin Fixed Paraffin Embedded

593 Background: Recently, we have shown that the Siemens Prognostic Score (SPS) based on mRNA expression of nine informative genes predicted outcome in node-positive (N+) patients with breast cancer (SABCS 2008, abstract 6044). The aim of this retrospective biomarker study was to examine the utility of the SPS in combination with TP53 expression to predict benefit from adjuvant taxane therapy. Methods: The 211 N+ patients included in this study were treated in the context of a randomized two-arm phase III study (E-T-CMF vs. E-CMF) investigating adjuvant dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was isolated from formalin-fixed, paraffin-embedded tissue samples, using a Siemens proprietary method, followed by kinetic one-step RT-PCR for assessment of mRNA expression of the nine SPS genes, TP53 and two normalization genes. The continuous SPS was calculated using a linear combination of expression values of the SPS genes. Patients were separated into a high- and low-risk group using a cutoff at the median of the SPS. Optimal cutoff for low or high TP53 expression was defined on the basis of a ROC curve in SPS high-risk patients. Distant metastasis-free survival (MFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Results: For patients with high SPS or high TP53 expression, we observed a trend for a better MFS in the E-T-CMF arm (SPS: p = 0.18; HR = 0.66; TP53: p = 0.23; HR = 0.67; n = 211). Combining both parameters, patients with high SPS and high TP53 expression (n = 44) had a significantly better MFS following E-T-CMF compared to E-CMF (5-year MFS 80% vs. 40%, p = 0.003, HR = 0.21; OS: p = 0.09; HR = 0.34). On the other hand, patients with high SPS and low TP53 expression (n = 32) showed a trend for a worse outcome with E-T-CMF (MFS: p = 0.09; HR = 3.54; OS: p = 0.35, HR = 1.90). Conclusions: Our prognostic algorithm combined with TP53 mRNA expression predicts the benefit from the addition of paclitaxel to E-CMF and might be used for identification of patients who should be considered for adjuvant taxane therapy. This hypothesis needs to be confirmed in an independent clinical study. [Table: see text]

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