Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins

2021 ◽  
pp. 153537022110104
Author(s):  
Mingfei Xu ◽  
Chaoyue Liu ◽  
Lulan Pu ◽  
Jinrong Lai ◽  
Jingjia Li ◽  
...  

Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan–Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan–Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xinyu Liu ◽  
Ying Liu ◽  
Qiangshan Wang ◽  
Siqi Song ◽  
Lingjun Feng ◽  
...  

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.


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 21 (19) ◽  
pp. 7427
Author(s):  
Iris Garrido-Cano ◽  
Vera Constâncio ◽  
Anna Adam-Artigues ◽  
Ana Lameirinhas ◽  
Soraya Simón ◽  
...  

MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analysed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. MiR-99a-5p expression levels were determined by quantitative real-time PCR in three independent cohorts of patients: (I) Discovery cohort: breast cancer tissues (n = 103) and healthy breast tissues (n = 26); (II) Testing cohort: plasma samples from 105 patients and 98 healthy donors; (III) Validation cohort: plasma samples from 89 patients and 85 healthy donors. Our results demonstrated that miR-99a-5p was significantly downregulated in breast cancer tissues compared to healthy breast tissues. Conversely, miR-99a-5p levels were significantly higher in breast cancer patients than in healthy controls in plasma samples from both testing and validation cohorts, and ROC curve analysis revealed that miR-99a-5p has good diagnostic potential even to detect early breast cancer. In conclusion, miR-99a-5p’s deregulated expression distinguished healthy patients from breast cancer patients in two different types of samples (tissues and plasma). Interestingly, expression levels in plasma were significantly lower in healthy controls than in early-stage breast cancer patients. Our findings suggest circulating miR-99a-5p as a novel promising non-invasive biomarker for breast cancer detection.


2021 ◽  
Author(s):  
Jun Wang ◽  
Xuebing Zhan ◽  
Qian Luo ◽  
Yunshu Kuang ◽  
Xiao Liang ◽  
...  

Abstract Background: Breast cancer is one of the most common tumors for women worldwide. Thrombospondins (THBSs) are reported to play important roles in various cellular processes and are involved in the occurrence and development of human cancers. However, the expression and prognostic value of THBSs family in breast cancer remain unclear.Methods: In this study, we examined the genes and protein expression levels of THBSs and their prognostic value by synthesizing several mainstream databases, including Oncomine, Human Protein Atlas (HPA), UALCAN, and KM Plotter. We also analyzed THBS interaction networks, genetic alterations, functional enrichment, and drug sensitivity with several publicly accessible databases, including GEPIA, GeneMANIA, STRING, cBioPortal, Metascape and NCI-60 database.Results: The results showed that the mRNA expression levels of THBS1, THBS2, THBS3, and THBS5 in breast cancer tissues were significantly higher than in normal tissues. The mRNA expression levels of THBS4 were different in different subtypes of breast cancer, and the protein expression levels of THBS1, THBS2, and THBS4 in breast cancer tissues were higher than in normal breast tissues. Survival analysis showed that breast cancer patients with high THBS1 gene expression showed worse overall survival (OS), relapse-free survival (RFS), and post-progression survival (PPS), and breast cancer patients with high THBS2 gene expression also showed worse RFS. Conversely, lower THBS3 levels predicted worse RFS, and lower THBS4 levels predicted worse OS, RFS, and distant metastasis-free survival (DMFS). Conclusions: These results suggest that THBSs may be potential biomarkers for breast cancer.


2013 ◽  
Vol 13 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Dagnija Kalniete ◽  
Miki Nakazawa-Miklasevica ◽  
Ilze Strumfa ◽  
Arnis Abolins ◽  
Arvids Irmejs ◽  
...  

Summary Introduction. MicroRNAs are a class of small, non-coding RNA molecules able to regulate gene expression at the post-transcriptional level through binding to the 3’-UTR of the targeted mRNA, thus suppressing translation of the mRNA. In various diseases, including malignancies, expression of microRNAs is altered. Moreover, the altered expression of the microRNAs correlates with clinical and pathophysiological features of cancer thus making them good candidates for prognostic/predictive markers. Aim of the study. The aim of this study was to determine expression level of five different microRNAs (miR-10b, miR-21, miR-29a, miR-31, and miR-214) in breast cancer tissues and to look for the differences in microRNA expression between distinct subtypes of breast cancer. Material and methods. Forty five breast cancer and corresponding resection line tissues (control tissues) were studied. Breast cancer tissues were classified into the subtypes of triple-negative (23), luminal-A (13), luminal-B (7), and HER2+ (2). Quantitative analysis of miR-10b, miR-21, miR-29a, miR-31, and miR-214 was performed by real-time PCR. The expression levels of microRNAs were normalized by the expression of the reference gene RNU6B. The event-free survival in regard of high and low expression levels of microRNAs were analyzed by Log-rank (Mantel Cox) and Gehan-Breslow-Wilcoxon tests. Results. Expression levels of four microRNAs (miR-21, miR-29a, miR-31, and miR-214) were significantly higher in cancer tissues than in corresponding resection line tissues. Breast cancer patients with low expression level of miR-21 showed a trend of better event-free survival than breast cancer patients with high expression level of miR-21; however, this trend did not reach statistical significance. In triple-negative tumor tissues, miR-21, miR-29a, and miR-31 showed significantly higher expression level than in luminal-A tumor tissues. Expression levels of miR-21 and miR-29a were significantly higher in triple-negative tumor tissues than in luminal-B tumor tissues. Conclusions. Breast cancer patients with high expression level of miR-21 in tumor tissues show a trend of worse event-free survival, though; this trend did not reach statistical significance. Different microRNA expression in distinct subtypes of breast cancer points to the genetic heterogeneity of breast cancer, different regulatory targets and signaling pathways


2019 ◽  
Vol 14 (1) ◽  
pp. 707-711
Author(s):  
Zhi Liu ◽  
Jing Zhou ◽  
Zhibao Wang ◽  
Zhiqiang Zhou

AbstractObjectiveTo analyze the expression and its clinical significance of the SEC24D gene in breast cancer.MethodsThe dataset of breast cancer were searched in the UALCAN database, and the data obtained were mined and combined with literature analysis.ResultsThe mRNA expression of the SEC24D gene in breast cancer tissues was significantly higher than that of breast normal tissues from the UALCAN database (P < 0.05). The promoter methylation levels of the SEC24D gene in breast cancer tissues were lower than that of breast normal tissues (P < 0.05). Survival analysis showed that the relapse-free survival of breast cancer patients with a higher expression of SEC24D gene was significantly worse than those patients with a lower expression of SEC24D (P < 0.05).ConclusionThe SEC24D gene has a high expression in breast cancer tissues and its expression level was related to the prognosis of breast cancer patients.


2021 ◽  
Author(s):  
chenchen Geng ◽  
Qian Pu ◽  
Shuxu Tian ◽  
Wenwen Geng ◽  
Haiyan Wang ◽  
...  

Abstract Background: To obtain a thorough comprehension of the profile and prognosis of activating transcription factor (ATF) family members in breast cancer.Method: We searched Oncomine, GEPIA, cBioPortal, Kaplan-Meier plotter, and CancerSEA databases to assess expression level, prognostic value, and functions of ATFs in breast cancer. Results: In breast cancer, we found that the expression levels of genes like ATF1, ATF5, and ATF6, were higher than in normal tissues. While the expression levels of ATF3, ATF4, ATF7 were lower in the former than in the latter. Similarly, the ATFs protein expressions were consistent with this in the Human Protein Atlas database. High expressions of ATF2, ATF4, and ATF6-7 were associated with good relapse-free survival. Increased expressions of ATF4 and ATF7 had high overall survival. Conversely, the mRNA expression of ATF1 was negatively correlated with distant metastasis-free survival. Similarly, high expression of ATF2 had reduced post-progression survival. Conclusions: ATF1 was a target of potential therapeutic interest for breast cancer, and ATF4 and ATF6-7 were potential prognostic factors in evaluating breast cancer.


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.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5344 ◽  
Author(s):  
Junnan Wang ◽  
Yiran Wang ◽  
Fei Long ◽  
Fengshang Yan ◽  
Ning Wang ◽  
...  

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.


Breast Care ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Kheirollah Yari ◽  
Zohreh Rahimi

Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.


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