Comprehensive Analysis of the Expression and Prognostic Significance of THBSs in Breast Cancer

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


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.


2012 ◽  
Vol 17 (6) ◽  
pp. 766-774 ◽  
Author(s):  
Chandra Bartholomeusz ◽  
Ana M. Gonzalez‐Angulo ◽  
Ping Liu ◽  
Naoki Hayashi ◽  
Ana Lluch ◽  
...  

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.


2010 ◽  
Vol 126 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Maria Aparecida Nagai ◽  
Renê Gerhard ◽  
José Humberto T. G. Fregnani ◽  
Suely Nonogaki ◽  
Regina Barbosa Rierger ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1887
Author(s):  
Stéphanie Blockhuys ◽  
Camilla Hildesjö ◽  
Hans Olsson ◽  
Linda Vahdat ◽  
Pernilla Wittung-Stafshede

Copper plays a key role in cancer metastasis, which is the most common cause of cancer death. Copper depletion treatment with tetrathiomolybdate (TM) improved disease-free survival in breast cancer patients with high risk of recurrence in a phase II clinical trial. Because the copper metallochaperone ATOX1 was recently reported to drive breast cancer cell migration and breast cancer migration is a critical factor in metastasis, we tested if ATOX1 expression levels in primary tumor tissue could predict the TM treatment outcome of breast cancer patients at high risk of recurrence. We performed ATOX1 immunohistochemical staining of breast tumor material (before TM treatment) of 47 patients enrolled in the phase II TM clinical trial and evaluated ATOX1 expression levels in relation with patient outcome after TM treatment. Our results show that higher ATOX1 levels in the tumor cell cytoplasm correlate with a trend towards better event-free survival after TM treatment for triple-negative breast cancer patients and patients at stage III of disease. In conclusion, ATOX1 may be a potential predictive biomarker for TM treatment of breast cancer patients at high risk of recurrence and should be tested in a larger cohort of patients.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chenjing Zhu ◽  
Otilia Menyhart ◽  
Balázs Győrffy ◽  
Xia He

Abstract Background Despite much effort on the treatment of breast cancer over the decades, a great uncertainty regarding the appropriate molecular biomarkers and optimal therapeutic strategy still exists. This research was performed to analyze the association of SPAG5 gene expression with clinicopathological factors and survival outcomes. Methods We used a breast cancer database including 5667 patients with a mean follow-up of 69 months. Kaplan-Meier survival analyses for relapse free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS) were performed. In addition, ROC analysis was performed to validate SPAG5 as a prognostic candidate gene. Results Mean SPAG5 expression value was significantly higher with some clinicopathological factors that resulted in tumor promotion and progression, including poor differentiated type, HER2 positive or TP53 mutated breast cancer. Based on ROC-analysis SPAG 5 is a suitable prognostic marker of poor survival. In patients who received chemotherapy alone, SPAG5 had only a moderate and not significant predictive impact on survival outcomes. However, in hormonal therapy, high SPAG5 expression could strongly predict prognosis with detrimental RFS (HR = 1.57, 95% CI 1.2–2.06, p = 0.001), OS (HR = 2, 95% CI 1.05–3.8, p = 0.03) and DMFS (HR = 2.36, 95% CI 1.57–3.54, p <  0.001), respectively. In addition, SPAG5 could only serve as a survival predictor in ER+, but not ER- breast cancer patients. Patients might also be at an increased risk of relapse despite being diagnosed with a lower grade cancer (well differentiated type). Conclusions SPAG5 could be used as an independent prognostic and predictive biomarker that might have clinical utility, especially in ER+ breast cancer patients who received hormonal therapy.


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